Methods and devices for endovascular embolization

ABSTRACT

The present disclosure describes an occlusion device and methods of delivering the occlusion device. The occlusion device can include an expandable structure configured to move between an unexpanded configuration and an expanded configuration. The expandable structure can be configured to have an expansion ratio of at least about 5:1. Further, the occlusion device can be configured to prevent substantially all fluid from flowing past the occlusion device when the occlusion device is in the expanded configuration in the vessel.

INCORPORATION BY REFERENCE TO ANY PRIORITY APPLICATIONS

This application is a divisional of U.S. application Ser. No.14/449,037, filed Jul. 31, 2014, titled “METHODS AND DEVICES FORENDOVASCULAR EMBOLIZATION,” which claims priority benefit under 35U.S.C. § 119(e) of U.S. Provisional Application No. 61/860,856, filedJul. 31, 2013, titled “METHODS AND DEVICES FOR ENDOVASCULAREMBOLIZATION,” U.S. Provisional Application No. 61/936,801, filed Feb.6, 2014, titled “METHODS AND DEVICES FOR ENDOVASCULAR EMBOLIZATION,” andU.S. Provisional Application No. 61/975,631, filed Apr. 4, 2014, titled“RETRACTABLE INTERLOCK DESIGN,” each of which is hereby incorporated byreference in its entirety.

BACKGROUND

Field

The present disclosure generally relates to apparatuses and methods foroccluding blood flow.

Description of the Related Art

A variety of endovascular devices have been proposed to occlude bloodflow for various applications in the vascular system. Early devices usedinflatable balloons, either non-detachable or later detachable, in orderto block vessels, for example, in the treatment of carotid-cavernousfistulas and saccular aneurysms (Serbinenko, Neurosurg. 41: 125-145,1974; Vopr. Neirokhir. July-August (4): 8-15. 1974; Vopr. Neirokhir.35(6): 3-9, 1971).

Typically made from latex or silicone, balloons are delivered to adesired location in a vessel, and then inflated to occlude the vessel.While other devices have since been developed, balloon occlusion remainsin use and is indicated for use in treating a variety oflife-threatening conditions, including for example, giant cerebral andskull base aneurysms (Wehman et al., Neurosurg., 59: S125-S138, 2006),traumatic and non-traumatic vessel injury or rupture (Luo et al., J.Chin. Med. Assoc. 66: 140-147, 2003; Hirai et al., Cardiovasc.Intervent. Radiol. 19: 50-52, 1996), vertebro-vertebral arteriovenousfistulas (Berguer et al., Ann. Surg. 196: 65-68, 1982), andpre-operative tumor resections.

Detachable balloons are also useful clinically in procedures outside ofneurological intervention. For example, balloons can be useful in flowreduction procedures such as shunt occlusion in patients withtransjugular intrahepatic portosystemic shunts and hepatic insufficiency(Kaufman et al., J. Vas. Interv. Radiol. 14: 635-638, 2003),intrahepatic arterioportal fistulas (Tasar et al., Clin. Imag. 29:325-330, 2005), treatment of varicoceles (White et al., Radiol. 139:327-334, 1981; Pollak et al., Radiol. 191: 477-482, 1994; Makita et al.,Radiol. 183: 575-577, 1992), shunt occlusion in patients with aBlalock-Taussig shunt (Reidy et al., Brit. Heart. J. 50: 101-103, 1983;DeSouza & Reidy, Clin. Radiol. 46: 170-175, 1992), obliteration ofpulmonary arteriovenous fistulas, arteriovenous malformations oraortopulmonary anastomoses (Pollak et al., Radiol. 191: 477-482, 1994;DeSouza & Reidy, Clin. Radiol. 46: 170-175, 1992; Reidy et al., Brit.Heart J 49: 284-287, 1983), coronary arteriovenous fistulas (Aydogan,Asian Cardiovasc. Thorac. Ann. 11: 63-67, 2003), or renal arteriovenousfistulas (Kadir et al., J. Urol. 129: 11-13, 1983; Marshall et al., J.Urol. 122: 237-239). Detachable balloons are also used in preoperativedevascularization before surgical resection of organs such as the kidney(Kadir et al., J. Urol. 129: 11-13, 1983).

Despite their usefulness, balloon occlusion devices suffer fromlimitations that affect their ease of use and safety. By its verynature, a balloon can expand and rupture, or alternatively it canspontaneously deflate over time (Hawkins & Szaz, Invest. Radiol. 22:969-972, 1987). Deflation is more common with latex balloons, with somestudies reporting 100% deflation rates (Perala et al., J. Vasc. Interv.Radiol. 9: 761-765, 1998). Spontaneous deflation can result in treatmentfailure and reoccurrence of the lesion (Pollak et al., Radiol. 191:477-482, 1994; Perala et al., J. Vasc. Interv. Radiol. 9: 761-765,1998).

Detachable balloon devices present other problems as well, and their usein the intracranial vasculature presents specific challenges. Forexample, balloons generally exhibit low trackability, meaning that theyare difficult to navigate, especially through tortuous vessels, such asthose commonly found in the intracranial circulation. In addition,premature (i.e., non-intentional) detachment from the delivery devicecan lead to adverse consequences such as cerebral artery blockage andstroke.

Even once in place, balloons can move forward during the process ofinflation, making placement of the unexpanded balloon in order toachieve precise positioning after inflation relatively difficult.Balloons that dislodge and migrate can require open skull surgeryespecially where the balloon has become lodged in a major vessel, forexample, in a cerebral artery (Cheng et al., Minim. Invasive Neurosurg.,49: 305-308, 2006).

An alternative approach has been to use hydrogel-coated coils in orderto produce rapid vascular occlusion (Kallmes & Cloft, Am. J.Neuroradiol. 25: 1409-1410, 2004). However, there remains a significantperiod between placement of the coil and formation of the occlusiveclot, even when using coated coils. This leads to concern that duringformation of the clot, distal clot migration can occur, with potentiallydevastating consequences such as stroke. Further, the geometricconfiguration and unpredictability of coil-based embolization preventsprecise occlusion of a short vascular segment. The risk of distalmigration of a clot is also of concern when treating high-flowperipheral lesions such as pulmonary arteriovenous fistulas (Ferro etal., Cardiovasc. Intervent. Radiol. 30: 328-331, 2007).

A further alternative is an expandable mechanical occlusion device suchas the Amplatzer Vascular Plug. Such devices are made of aself-expanding Nitinol mesh, and can be deployed intravascularly toblock flow through a vessel by inducing formation of a clot. However,this device does not produce immediate occlusion. Further, the devicemay not produce a chronic occlusion leading to residual patency of thetarget vessel. The device is also limited by it navigability, andplacement precision, which limits its utility to use in performingocclusions below the base of the skull (Ross & Buciuc, Amer. J.Neurorad. 28(2): 385-286, 2007).

Thus, notwithstanding the various efforts in the past, there remains aneed for devices and methods for rapid, well-controlled, safe, andeffective vessel occlusion.

SUMMARY

Certain aspects of this disclosure are directed toward an endovascularocclusion device. The device can include an expandable tubular framehaving at least one closed end and an occlusive membrane extendingacross at least the closed end. Further, the occlusion device has anexpansion ratio of at least about 5:1, at least about 6:1, or at leastabout 7:1. The occlusion device can also include a guidewire lumen, forremovably receiving a guidewire therethrough.

The guidewire lumen may be provided with a valve to block blood flowtherethrough following removal of the guidewire. The valve may comprisea polymeric membrane, such as in the form of a collapsible tubeextending in the upstream direction. The tube is collapsible under bloodpressure.

In the above-mentioned aspect, the device can have an unconstrainedexpanded diameter of at least about 1.5 mm, which can be deployed from a0.7 mm (0.027″) or smaller inside diameter lumen. In certain aspects,the device can have an unconstrained expanded diameter of at least about6.0 mm, which can be deployed from a 0.7 mm (0.027″) or smaller insidediameter lumen.

Certain aspects of this disclosure are directed toward an endovascularocclusion device having an expandable occlusive element for expansionwithin and occlusion of a vessel. The occlusive element can have anexpansion ratio of at least about 5:1.

Certain aspects of this disclosure are directed toward an occlusiondevice for occluding a vessel. The occlusion device can include anexpandable structure such as an hourglass configuration including afirst lobe or end portion, a second lobe or end portion, and a middle orneck portion therebetween. The expandable structure can move between anunexpanded configuration and an expanded configuration. The expansionratio of the expandable structure can be at least about 3:1, preferablyat least about 5:1, and, in some instances, at least about 7:1, forexample, about 8:1. Further, the occlusion device can be configured toprevent substantially all fluid from flowing past the occlusion devicewhen the expandable structure is in the expanded configuration in thevessel.

In the above-mentioned aspect, a largest diameter of the expandablestructure in the unexpanded configuration is less than or equal to about2 mm, such as between about 1.25 mm and about 1.75 mm, preferably lessthan or equal to about 1.5 mm.

In any of the above-mentioned aspects, the expandable structure caninclude a uniform or a non-uniform diameter across a length of theexpandable structure. For example, a diameter of the second end portioncan be substantially larger than a diameter of the first end portion. Asanother example, a diameter of the middle portion can be substantiallylarger or smaller than a diameter of the first end portion and adiameter of the second end portion. In yet another example, the firstand second end portions of the expandable structure can be tapered.

In any of the above-mentioned aspects, the occlusion device can includea cover membrane carried by at least one of the first and second endportions. For example, the cover can only be carried by the first endportion. As another example, the cover can surround the first and secondend portions, and the middle portion can remain uncovered. In yetanother example, the cover can surround substantially the entireexpandable structure.

In any of the above-mentioned aspects, the occlusion device can includea cover having a thickness of less than or equal to about 30 microns.The cover can include a cover material including, but not limited to,TecoThane, nylon, PET, Carbothane (Bionate), fluoropolymer, SIBS, andPLGA.

In certain aspects, the occlusion device can include a drum headdisposed within the first end portion of the expandable structure, suchthat the drumhead prevents fluid flow through the first end portion. Insome instances, the occlusion device can include a cover surrounding thedrumhead.

In any of the above-mentioned aspects, the expandable structure caninclude one or more strands. The one or more strands can be woven toform a wall pattern. In some instances, the wall pattern can besubstantially uniform across a length of the expandable structure.Alternatively, the expandable structure can include a laser cut tubularelement. In some instances, a wall pattern of the second end portionincludes a greater amount of open area than a wall pattern of the firstend portion.

In any of the above-mentioned aspects, the occlusion device can includefeatures to prevent migration of the occlusion device after deployment.For example, the occlusion device can include one or more anchorsdisposed along an uncovered portion, such as an end lobe or middleportion the expandable structure. As another example, if the occlusiondevice is braided, each of the one or more strands includes strand ends.At least some of the strand ends can remain exposed to anchor theocclusion device to the vessel wall.

Certain aspects of the disclosure are directed toward a delivery systemfor delivering an occlusion device. The delivery system can include anouter catheter and an inner catheter axially movable within the outercatheter. The inner catheter can deliver the occlusion device out of theouter catheter. The outer catheter preferably includes an outer diameterof less than or equal to about 2.0 mm, preferably less than or equal toabout 1.67 mm (5 F). In some instances, the delivery system can includea support tube axially disposed between the outer catheter and the innercatheter, for example, when the inner catheter is configured to carrythe expandable structure on a distal portion of the inner catheter. Theocclusion device can include any of the above-mentioned occlusion deviceaspects.

Certain aspects of this disclosure are directed toward a method ofoccluding a vessel. The method can include positioning a delivery systemin the vessel and deploying a single occlusion device from the deliverysystem. In some instances, the positioning step can include advancingthe delivery system over a guide wire. The delivery system can includeany of the above-mentioned delivery system aspects. Further, the singleocclusion device can include any of the above-mentioned occlusion deviceaspects.

Certain aspects of the disclosure are directed toward an endovascularocclusion device for occluding blood flow through a vessel. Theendovascular occlusion device can include an expandable frame and amembrane carried by the frame. The frame and the membrane can bedimensioned for deployment from a tube having an inside diameter of lessthan or equal to about 2 mm, preferably less than or equal to about 1.5mm, such as less than or equal to about 1.3 mm. The tube can have anoutside diameter of less than or equal to about 2 mm, preferably lessthan or equal to about 1.67 mm. Further, the frame and the membrane canbe expandable to a diameter of at least about 8 mm following deploymentfrom the tube. The membrane can have a porosity that achieves areduction in blood flow of at least about 80% within about five minutesof deployment from the tube in a blood vessel, preferably within abouttwo minutes of deployment from the tube in a blood vessel or withinabout one minute of deployment from the tube in a blood vessel. Incertain aspects, the occlusion device can be configured to achieve totalocclusion within about two minutes of deployment from the tube in ablood vessel, preferably within about one minute of deployment from thetube in a blood vessel. In certain aspects, the occlusion device canachieve 80% occlusion in less than or equal to about 30 seconds, 90%occlusion in less than or equal to about 3 minutes, and/or 100%occlusion in less than or equal to about 5 minutes according to theOcclusion Protocol described below. Due to the physical or mechanicalocclusion mechanism of action, the foregoing occlusion characteristicsare unaffected by the patients' anticoagulant status.

In the above-mentioned endovascular occlusion device, the occlusiondevice can have an expansion ratio of at least about 6:1, preferably atleast about 7:1.

In any of the above-mentioned endovascular occlusion devices, theocclusion device can be delivered over a 0.018-inch or smallerguidewire.

In any of the above-mentioned endovascular occlusion devices, themembrane can include an average pore size of no more than about 100microns, preferably no more than about 50 microns.

In any of the above-mentioned endovascular occlusion devices, the devicecan have an average COP across a diameter between about 2.5 mm and about8.0 mm (e.g., a diameter between about 3.0 mm and about 8.0 mm) ofbetween about 20 mmHg and about 250 mmHg, such as between about 30 mmHgand about 140 mmHg, between about 30 mm Hg and 80 mmHg, between aboutbetween about 70 mmHg and 100 mmHg, between about 90 mmHg and 120 mmHg,or between about 100 mmHg and 140 mmHg.

Another aspect of the disclosure is directed toward an endovascularocclusion device for achieving mechanical occlusion of blood flow in avessel without requiring biological processes to achieve occlusion. Theocclusion device can include an expandable support structure carrying aporous membrane. The membrane can be configured to obstruct blood flowthrough the vessel when the support structure is in an expandedconfiguration. The membrane can have an average pore size of no morethan about 100 microns, preferably no more than about 50 microns.

In the above-mentioned occlusion device, the membrane can include anaverage thickness of no more than about 30 microns.

In any of the above-mentioned endovascular occlusion devices, theocclusion device can be deliverable from a lumen having an insidediameter less than or equal to about 2 mm, preferably less than or equalto about 1.67 mm.

In any of the above-mentioned endovascular occlusion devices, the devicecan have an average COP across a diameter of 2.5 mm to 8.0 mm (e.g.,between about 3.0 mm and about 8.0 mm) of between about 20 mmHg andabout 250 mmHg, such as between about 30 mmHg and about 140 mmHg,between about 30 mm Hg and 80 mmHg, between about between about 70 mmHgand 100 mmHg, between about 90 mmHg and 120 mmHg, or between about 100mmHg and 140 mmHg.

Yet another aspect of the disclosure is directed toward an endovascularocclusion device for occluding blood flow through a vessel. Theocclusion device can include a frame that is expandable through a rangefrom a first, compressed diameter to a second, maximum expandeddiameter. The range of expansion can be sufficient to occlude bloodvessels having inside diameters anywhere within the range from about 2.5mm to about 8 mm, such as within the range from about 3 mm to about 7mm.

Certain aspects of the disclosure are directed toward a low crossingprofile, high dynamic range endovascular occlusion device having anopening for receiving a guidewire therethrough. The occlusion device canbe expandable from a first diameter for transvascular navigation withina deployment catheter to a deployment site, to a second diameter foroccluding a vessel following deployment from the catheter. The cathetercan include a diameter of no greater than about 5 French and theexpansion ratio can be at least about 6×, preferably at least about 8×.In certain aspects, the occlusion device can include an expandable frameand an occlusion membrane.

In any of the above-mentioned low crossing profile occlusion devices,the occlusion device can be deliverable from a lumen having an insidediameter of less than or equal to about 2 mm, preferably less than orequal to about 1.67 mm.

In any of the above-mentioned low crossing profile occlusion devices,the occlusion device can be delivered over a 0.018 inch or smallerguidewire.

In any of the above-mentioned low crossing profile occlusion devices,the membrane can include an average pore size of no more than about 100microns, preferably no more than about 50 microns, such as an averagepore size between about 5 microns and 10 microns or between about 10microns and 15 microns.

Certain aspects of the disclosure are directed toward an endovascularocclusion deployment system for navigating tortuous vasculature todeploy an occlusion device at a target site in a vessel. The deploymentsystem can include an elongate, flexible tubular body, having a proximalend, a distal end, and a diameter of no more than about 5 French. Thedeployment system can also include an occlusion device releasablycarried in the distal end of the tubular body. Further, the occlusiondevice has an expansion ratio of at least about 5 to 1. The distal endof the tubular body can be advanced to the target vessel with sufficienttrackability as determined by the Trackability Protocol described below(e.g., access a minimum of 4 cm into the right hepatic artery). Further,the occlusion device can include any of the aforementioned occlusiondevice aspects.

Another aspect of the disclosure is directed toward a low crossingprofile, high dynamic range endovascular occlusion device with lowelongation. The occlusion device can be expandable from a first diameterfor transvascular navigation within a deployment catheter to adeployment site to a second diameter for occluding a vessel followingdeployment from the catheter. The catheter can have a diameter of lessthan or equal to about 5 French. The occlusion device can have anexpansion ratio of at least about 5×, and the elongation of the devicebetween the first diameter and the second diameter can be no more thanabout 20%. Further, the occlusion device can include any of theaforementioned occlusion device aspects.

Yet another aspect of the disclosure is directed toward a migrationresistant endovascular occlusion device for occluding blood flow througha vessel. The occlusion device can include an expandable frame and amembrane carried by the frame. The frame and membrane can be dimensionedfor deployment from a tube having an inside diameter of no more thanabout 2 mm and can be expandable to a diameter of at least about 8 mmfollowing deployment from the tube. The occlusion device can exhibit amigration of less than about 5.0 mm at about 120 mmHg, preferably at 200mmHg or 300 mmHg, as determined by the Migration Protocol describedherein. Further, the occlusion device can include any of theaforementioned occlusion device aspects.

Another aspect of the disclosure is directed toward an endovascularocclusion deployment system with contrast injection capability fornavigating tortuous vasculature to deploy an occlusion device at atarget site in a vessel. The deployment system can include an elongate,flexible tubular body, having a proximal end, a distal end, and adiameter of no more than about 5 French. An occlusion device can bereleasably carried in the distal end of the tubular body, the occlusiondevice having an expansion ratio of at least about 5 to 1. Thedeployment system can also include a contrast injection port on thebody, proximal to the occlusion device. The contrast injection portpermits injection of contrast while the occlusion device is in anexpanded configuration and prior to release of the occlusion device fromthe tubular body. In certain aspects, the distal end of the tubular bodycan be advanced to the target vessel with sufficient trackability asdetermined by the Trackability Protocol described herein. Further, theocclusion device can include any of the aforementioned occlusion deviceaspects.

For purposes of summarizing the disclosure, certain aspects, advantages,and features of the inventions have been described herein. It is to beunderstood that not necessarily any or all such advantages are achievedin accordance with any particular embodiment of the inventions disclosedherein. No aspects of this disclosure are essential or indispensable.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments are depicted in the accompanying drawings forillustrative purposes, and should in no way be interpreted as limitingthe scope of the embodiments. Furthermore, various features of differentdisclosed embodiments can be combined to form additional embodiments,which are part of this disclosure.

FIG. 1A illustrates a delivery system for delivering an occlusiondevice.

FIG. 1A-1 illustrates an enlarged view of a distal portion of thedelivery system shown in FIG. 1A.

FIG. 1B-1 illustrates an embodiment of an outer catheter that can beused with the delivery system shown in FIG. 1A.

FIG. 1B-2 illustrates an enlarged view of the working length of theouter catheter shown in FIG. 1B-1.

FIG. 1B-3 illustrates an embodiment of an inner catheter that can beused with the delivery system shown in FIG. 1A.

FIG. 1B-4 illustrates an enlarged view of a distal portion of the innercatheter shown in FIG. 1B-3 through line 1B-3-1B-3.

FIG. 1C-1 illustrates an embodiment of a delivery system having a pusherinterlock assembly in a locked configuration.

FIG. 1C-2 illustrates the pusher interlock assembly shown in FIG. 1C-1in an unlocked configuration.

FIG. 1C-3 illustrates an embodiment of an occlusion device having aportion of the pusher interlock assembly shown in FIG. 1C-1 and detachedfrom the delivery system.

FIG. 1D-1 illustrates another embodiment of a delivery system having athreaded interlock assembly.

FIG. 1D-2 illustrates an enlarged view of the threaded interlockassembly through line 1D-2 shown in FIG. 1D-1.

FIG. 1E-1 illustrates another embodiment of a delivery system having aninterlock catheter.

FIG. 1E-2 illustrates an enlarged view of a portion of the deliverysystem shown in FIG. 1E-1 taken through line 1E-2 to 1E-4 with theinterlock assembly in a locked configuration.

FIG. 1E-3 illustrates an enlarged view of a portion of the deliverysystem shown in FIG. 1E-1 taken through line 1E-2 to 1E-4 with theinterlock assembly in an unlocked configuration.

FIG. 1E-4 illustrates an enlarged view of a portion of the deliverysystem shown in FIG. 1E-1 taken through line 1E-2 to 1E-4 with theocclusion device detached.

FIG. 1E-5 illustrates a cross-section of FIG. 1E-2 taken through line1E-5 to 1E-5 without the occlusion device.

FIG. 1E-6 illustrates a cross-section of FIG. 1E-4 taken through line1E-6 to 1E-6.

FIG. 2A illustrates another embodiment of a delivery system.

FIG. 2B illustrates an enlarged view of a distal portion of the deliverysystem shown in FIG. 2A through line B prior to deployment.

FIG. 2C illustrates the distal portion of the delivery system shown inFIG. 2A with the distal lobe of the occlusion device partially deployed.

FIG. 2CC illustrates an enlarged cross-section of the distal portionshown in FIG. 2C taken through line CC.

FIG. 2D illustrates the distal portion of the delivery system shown inFIG. 2A with the distal lobe of the occlusion device fully deployed.

FIG. 2DD illustrates an enlarged cross-section of the distal portionshown in FIG. 2D taken through line DD.

FIG. 2E illustrates the distal portion of the delivery system shown inFIG. 2A with the distal lobe of the occlusion device partiallyretracted.

FIG. 2EE illustrates a cross-section of the distal portion shown in FIG.2E taken through line EE.

FIG. 2F illustrates the distal portion of the delivery system shown inFIG. 2A with a majority of the occlusion device deployed.

FIG. 2FF illustrates a cross-section of the distal portion shown in FIG.2F taken through line FF.

FIG. 2G illustrates the distal portion of the delivery system shown inFIG. 2A with the occlusion device fully deployed.

FIG. 2H illustrates a cross-section of the occlusion device shown inFIG. 2G with the inner catheter partially retracted.

FIG. 2HH illustrates an enlarged view a tubular membrane portion of theocclusion device shown in FIG. 2H taken through line HH.

FIG. 2I illustrates a cross-section of the occlusion device shown inFIG. 2H with the inner catheter further retracted.

FIG. 2II illustrates an enlarged view of the tubular membrane portion ofthe occlusion device shown in FIG. 2I taken through line II.

FIG. 2J illustrates a cross-section of the occlusion device shown inFIG. 2I with the inner catheter further retracted.

FIG. 2JJ illustrates an enlarged view of the tubular membrane portion ofthe occlusion device shown in FIG. 2J taken through line JJ.

FIG. 2K illustrates a cross-section of the occlusion device shown inFigure JJ with the delivery system fully withdrawn from the occlusiondevice.

FIG. 2L illustrates the inner catheter of the delivery system shown inFIG. 2A.

FIG. 2M illustrates an enlarged view of a distal portion of the innercatheter shown in FIG. 2L.

FIG. 2N illustrates a cross-section of a distal portion through line 2Nof the outer catheter shown in FIG. 2M.

FIG. 2O illustrates the outer catheter of the delivery system shown inFIG. 2A for contrast dye injection.

FIG. 2P illustrates an enlarged view of a working length of the outercatheter shown in FIG. 2O.

FIG. 2Q illustrates another deployment system having an interlockattachment member interfacing with an occlusion device.

FIG. 2R illustrates another deployment system having an interlockattachment member released from the occlusion device.

FIG. 2S illustrates an embodiment of a delivery system for delivering anocclusion device having a test balloon.

FIGS. 3A-3F illustrate another delivery system and an occlusion devicehaving a tapered proximal end.

FIGS. 4A-4F illustrate yet another delivery system and a generallycylindrical occlusion device.

FIG. 4G illustrates an enlarged view of the occlusion device shown inFIGS. 4A-4F.

FIGS. 5A-5F illustrate a delivery system and another generallycylindrical occlusion device.

FIG. 5G illustrates an enlarged view of the occlusion device shown inFIGS. 5A-5F.

FIG. 6 illustrates a partially covered, hourglass-shaped occlusiondevice.

FIG. 7A illustrates a partially covered occlusion device having taperedends.

FIG. 7B illustrates a fully covered occlusion device having taperedends.

FIG. 8 illustrates an expandable structure having a non-uniformdiameter.

FIG. 9A illustrates another expandable structure having tapered ends.

FIGS. 9B-9C illustrate the expandable structure in FIG. 9A partiallycovered with a cover.

FIG. 10A illustrates a fully covered occlusion device having a first,closed end portion and a second, opened end portion.

FIG. 10B illustrates a partially covered occlusion device having afirst, closed end portion and a second, opened end portion.

FIGS. 11A-11C illustrate different views of an occlusion device having adrumhead and a cover.

FIG. 12A illustrates an embodiment of an occlusion device having anasymmetrical hourglass shape.

FIG. 12B illustrates the embodiment of the occlusion device shown inFIG. 12A having a radiopaque marker secured to a proximal end of theocclusion device.

FIG. 12C illustrates an enlarged view of a cell structure of theocclusion device shown in FIG. 12A.

FIG. 12D illustrates a schematic view of the occlusion device shown inFIG. 12A in a collapsed configuration.

FIG. 12E illustrates an enlarged view of an end portion of the occlusiondevice shown in FIG. 12D through line A.

FIG. 12F illustrates a schematic cross-section of the occlusion deviceshown in FIG. 12A having a valve-like tubular section.

FIG. 12G illustrates an end view of the occlusion device shown in FIG.12F with the tubular section in an open configuration.

FIG. 12H illustrates the occlusion device shown in FIG. 12G with thetubular section in a closed configuration.

FIG. 13A illustrates another embodiment of an hourglass-shaped occlusiondevice in an expanded configuration with a portion of the membraneremoved to show the tubular portion of the membrane.

FIG. 13B illustrates the occlusion device shown in FIG. 13A in anunexpanded configuration.

FIG. 13C illustrates an end view of the occlusion device shown in FIG.13A.

FIG. 13D illustrates an enlarged view of a strut ending at a distalportion of the occlusion device shown in FIG. 13A through line 13D.

FIG. 13E illustrates an enlarged view of a strut ending at a proximalportion of the occlusion device shown in FIG. 13A through line 13E.

FIG. 13F illustrates the hourglass-shaped occlusion device shown in FIG.13A, annotated to illustrate the curvature of the proximal and distalstruts.

FIGS. 14A to 14U illustrate alternative embodiments of providing bendingflexibility to the occlusion device.

FIG. 15A illustrates another embodiment of the occlusion device havingtapered ends.

FIG. 15B illustrates the embodiment of the occlusion device shown inFIG. 15B having a marker coil.

FIG. 16 illustrates yet another embodiment of the occlusion devicehaving a closed proximal end and an open distal end.

FIG. 17 illustrates another embodiment of the occlusion device having awedge-shaped end portion.

FIG. 18 is a block diagram of a method of coating an occlusion devicedescribed herein.

FIG. 19A illustrates a Trackability Protocol fixture.

FIG. 19B illustrates a model for the Trackability Protocol fixture.

FIG. 19C illustrates an enlarged view of a portion of the model shown inFIG. 19A through circle 19C.

FIG. 19D illustrates an enlarged view of a portion of the model shown inFIG. 19A through circle 19D.

FIG. 19E illustrates an enlarged view of a portion of the model shown inFIG. 19A through circle 19E.

FIG. 19F illustrates another model for the Trackability Protocolfixture.

FIG. 19G illustrates a measurement of the linear distance between thedistal tip of the delivery system to a predefined location in the modelshown in FIG. 19A.

FIG. 19H illustrates another model of the anatomic model that can beused to assess delivery, deployment, and retraction.

FIG. 20A illustrates a Migration Protocol test fixture.

FIG. 20B illustrates a mock 8 mm curved vessel.

FIG. 20C illustrates a mock 3 mm curved vessel.

FIG. 20D illustrates a vessel that can be used in connection with thetest fixture shown in FIG. 20A.

FIG. 21 illustrates a schematic of an Occlusion Protocol test fixture.

FIGS. 22A and 22B illustrates different steps of the Occlusion Protocol.

FIG. 23 illustrates a schematic of an Injection Protocol test fixture.

DETAILED DESCRIPTION

The following discussion is presented to enable a person skilled in theart to make and use one or more embodiments of the invention. Thegeneral principles described herein may be applied to embodiments andapplications other than those detailed below without departing from thespirit and scope of the invention. Therefore the present invention isnot intended to be limited to the embodiments shown, but is to beaccorded the widest scope consistent with the principles and featuresdisclosed or suggested herein.

Delivery System

FIGS. 1A and 1A-1 illustrate an exemplary delivery system 100 fordelivering any of the occlusion devices illustrated herein. The deliverysystem 100 can include an outer catheter 110 and an inner catheter 120extending through the outer catheter 110. Although primarily describedin the context of an intravascular embolic deployment catheter with asingle central lumen, catheters of the present invention can readily bemodified to incorporate additional structures, such as permanent orremovable column strength enhancing mandrels, two or more lumen such asto permit drug or irrigant infusion or aspiration or radiation deliveryor to supply inflation media to an inflatable balloon, or combinationsof these features, as will be readily apparent to one of skill in theart in view of the disclosure herein.

The catheters and occlusion devices disclosed herein may readily beadapted for use throughout the body wherever it may be desirable tointroduce an occluder. For example, occlusion devices may be deployedthroughout the coronary and peripheral vasculature, neurovasculature,the gastrointestinal tract, the urethra, ureters, Fallopian tubes, andother lumens and potential lumens, as well.

Generally, the occlusion devices described herein can be delivered via alow profile outer catheter 110 (e.g., having an outer diameter fromabout 2.8 F (0.93 mm) to about 6 F (2.0 mm), typically from about 3 F(1.0 mm) to about 5 F (1.67 mm), preferably less than about 5 F (1.67mm), such as about 4.7 F (1.57 mm)). Further, the occlusion devicesdescribed herein can be delivered over a guide wire having a diameter ofat least about 0.010 inches and/or less than or equal to about 0.02inches to facilitate trackability of the delivery catheter, while stillutilizing a low profile delivery catheter. For example, the guide wirecan have a diameter of about 0.01 inches, 0.014 inches, or about 0.018inches.

The outer catheter 110 can generally include an elongate tubular body116 extending between a proximal end 112 and a distal end 114. Thelength of the tubular body 116 depends upon the desired application. Forexample, lengths in the area of from about 120 cm to about 140 cm ormore are typical for use in femoral access percutaneous transluminalcoronary applications. Further, the outer catheter 110 should havesufficient working length to reach the target vessel. The minimumworking length for these applications can be at least about 75 cm about90 cm, or at least about 100 cm, but no more than about 175 cm.Intracranial or other applications may call for a different cathetershaft length depending upon the vascular access site, as will beunderstood in the art. Deployment catheters adapted for intracranialapplications generally have a total length in the range from 60 cm to250 cm, usually from about 135 cm to about 175 cm.

In general, neurovascular devices may be deployable from cathetershaving a length of at least about 120 cm or 125 cm or greater, to allowaccess to the carotid artery bifurcation and above. Devices configuredfor coronary or peripheral applications may have shorter deliverycatheters and other dimensional modifications as are understood in theart.

The catheters of the present invention may be composed of any of avariety of biologically compatible polymeric resins having suitablecharacteristics when formed into the tubular catheter body segments.Exemplary materials include polyvinyl chloride, polyethers, polyamides,polyethylenes, polyurethanes, a polycarbonate blend, copolymers thereof,and the like. Optionally, the tubular body may be reinforced with ametal or polymeric braid or other conventional reinforcing layer.

The catheter material should be selected such that the delivery systemdemonstrates acceptable trackability and deployment forces to enableaccess to the target vessel and delivery of the implant to the targetvascular. Further, the material of the outer catheter 110 should besufficient to maintain its integrity during flushing and hemostasis. Forexample, the outer catheter 110 should be able to resist a pressure ofat least about 45 psi/min.

Further, the outer catheter 110 must have sufficient structuralintegrity (e.g., column strength or “pushability”) to permit the outercatheter 110 to be advanced to distal locations without buckling orundesirable bending of the tubular body 116. The ability of the outercatheter 110 to transmit torque may also be desirable, such as to avoidkinking upon rotation, to assist in steering. The outer catheter 110,and particularly the distal portion, may be provided with any of avariety of torque and/or column strength enhancing structures. Forexample, axially extending stiffening wires, spiral wrapped supportlayers, and/or braided or woven reinforcement filaments may be builtinto or layered on the tubular body 116.

The delivery system 100 and its variants described herein are capable ofpenetrating the target vessel by at least 4 cm, such as between about 4cm and 6 cm, for example, at least 5 cm, or preferably at least about5.5 cm as determined by the Trackability Protocol described below.

The proximal portion of the outer catheter 110 may have a shore hardnessin the range from 50 D to 100 D, often being about 70 D to 80 D.Usually, the proximal portion of the outer catheter 110 will have aflexural modulus from 20,000 psi to 1,000,000 psi, preferably from100,000 psi to 600,000 psi. The distal portion of the outer catheter 110will be sufficiently flexible and supple so that it may navigate thepatient's distal vasculature. In highly flexible embodiments, the shorehardness of the distal portion may be in the range from about 20 A toabout 100 A, and the flexural modulus for the distal portion may be fromabout 50 psi to about 15,000 psi.

The outer catheter 110 may be produced in accordance with any of avariety of known techniques for manufacturing interventional catheterbodies, such as by extrusion of appropriate biocompatible polymericmaterials. At least a proximal portion or all of the length of outercatheter 110 may comprise a polymeric or metal spring coil, solid walledhypodermic needle tubing, or braided reinforced wall, as is known in themicrocatheter arts.

The proximal end 112 of outer catheter 110 can include a manifold 118having one or more access ports as is known in the art. Generally, themanifold 118 can include a guidewire port. Additional access ports maybe provided as needed, depending upon the functional capabilities of thecatheter. The manifold 118 can be compatible with luer connections fromrelated accessories. Further, the manifold 118 may be injection moldedfrom any of a variety of medical grade plastics, or formed in accordancewith other techniques known in the art.

Manifold 118 can also include a control (not shown), for controllingdeployment of the occlusion device. The control may take any of avariety of forms depending upon the mechanical structure of the support.For example, the control can include a slider switch, which can connectto the inner catheter 120. Distal axial advancement of the slider switchcan produce an axial advance of the connected feature. When theocclusion device advances from the distal end of the outer catheter 110,the occlusion device can move from the reduced diameter to the enlargeddiameter.

Any of a variety of controls may be utilized, including switches,levers, rotatable knobs, pull/push wires, and others that will beapparent to those of skill in the art in view of the disclosure herein.

The outer catheter 110 can define a lumen through which the innercatheter 120 can move axially. The inner catheter 120 can include aproximal end 122 and a distal end 124. Similar to the outer catheter110, the inner catheter 120 can include a manifold 126 disposed at theproximal end 122 of the inner catheter 120. The manifold 126 can beconfigured to control movement of the inner catheter 120, deployment ofthe occlusion device, and/or fluid flow through the inner catheter 120.The inner catheter 120 should be sufficiently long to deliver theocclusion device out of the distal end 114 of the outer catheter 110.Further, the inner catheter 120 can include a material exhibiting any ofthe material properties described in connection with the outer catheter110.

The inner catheter 120 can define a lumen through which a conventionalguide wire can move axially. In an alternate configuration, the outercatheter 110 can include a second lumen having a guide wire axiallymovable therein. In either scenario, the guide wire lumen should besufficiently large to accommodate a guide wire 128 having a diameterbetween about 0.25 mm and about 0.5 mm. As shown in FIG. 1A, the guidewire 128 can include a hub 130 disposed at a proximal end of the guidewire 128.

Avoiding a tight fit between the guide wire 128 and inside diameter ofguidewire lumen enhances the slideability of the delivery system 100over the guidewire. In ultra-small diameter catheter designs, it may bedesirable to coat the outside surface of the guidewire 128 and/or theinside surface of the inner catheter 120 with a lubricous coating tominimize friction as the inner catheter 120 is axially moved withrespect to the guidewire 128. A variety of coatings may be utilized,such as Parylene, Teflon, silicone rubber,polyimide-polytetrafluoroethylene composite materials, or others knownin the art and suitable depending upon the material of the guidewire orinner tubular wall.

The delivery system 100 can include different features depending onwhether the occlusion device is self-expanding or balloon expandable.For example, if the occlusion device is balloon expandable, the innercatheter 120 can carry the occlusion device on a balloon (not shown).

For example, if the occlusion device is self-expanding, the occlusiondevice can be constrained by a distal portion of the outer catheter 110,and the inner catheter 120 can push the occlusion device out from thedistal end 114 of the catheter 110. As another example, as shown in FIG.3F, the delivery system 100 can include a support tube 134 axiallydisposed between the outer catheter 110 and the inner catheter 120. Thesupport tube 134 can move axially to push the occlusion device off theinner catheter 120. The force necessary to push the occlusion device offthe inner catheter 120 can be less than or equal to about 5 N, forexample, within about 0.25 N of about 4.5 N or within about 0.25 N ofabout 4.0 N.

Other conventional mechanisms can be used to release the occlusiondevice, including, but not limited to, a ratcheting mechanism, anelectrolytically erodible attachment, involuted deployment, a threadedattachment, or other torque releasing attachment.

In some situations, it may be necessary to resheath the occlusion deviceto deliver the occlusion device to the target vessel. The deliverysystem 100 can be configured to resheath and reposition the occlusiondevice after deployment, but before release. Prior to release, the innercatheter 120 can be retracted to pull the occlusion device back into theouter catheter 110. The retraction force necessary to retract theocclusion device should be less than or equal to about 5 N, for example,between about 3 N and about 4 N, or between about 3.5 N and about 4.5 N.The interlock interference feature can have a dimension between about0.15 mm and about 0.25 mm, for example, within about 0.02 mm of about0.2 mm.

The delivery system 100 may further comprise other components, such asradiopaque fillers, colorants, reinforcing materials, reinforcementlayers, such as braids and helical reinforcement elements, or the like.In particular, at least the proximal portion may be reinforced in orderto enhance its column strength and torqueability while preferablylimiting its wall thickness and outside diameter. Further, radiopaquemarkers may be positioned on the inner and/or outer catheters 120, 110to monitor the delivery system 100 during the procedure.

Fluoroscopic guidance can be used to monitor the delivery of theocclusion device. For example, the delivery system can includeradiopaque features that allow for their fluoroscopic visualizationduring delivery, deployment, and/or retraction. Usually, the deliverysystem can include marker bands or coiled wires disposed along one ormore of the outer catheter 110, inner catheter 120, and the guide wire128. The bands or coils can include a minimum thickness of at leastabout 0.02 mm and a minimum length of about 0.5 mm. Suitable markerbands can be produced from any number of a variety of materials,including platinum, gold, tantalum, and tungsten/rhenium alloy.Preferably, the radiopaque metal band will be recessed in an annularchannel formed in the tubular body.

FIGS. 1B-1 and 1B-2 illustrate a possible embodiment the outer catheter110 of the delivery system. The outer catheter permits contrast dye tobe injected through the delivery system and can be used to determine theposition of the occlusion device before detaching the occlusion devicefrom the delivery system.

The outer catheter 110 can have a working length of about 120 cm or anyother suitable working length described above. An internal diameter ofthe outer catheter 110 can be less than or equal to about 0.10 inches,such as about 0.05 inches. The distal end 114 of the outer catheter 110can have a reduced diameter between about 0.02 inches and about 0.04inches. The outer catheter 110 can include a plurality of openings 121(e.g., at least two, five, six, eight, or more openings) disposed near adistal end 114 of the outer catheter 110, such that contrast dye can bereleased near the proximal side of the occlusion device. The placementof the openings 121 can remove the pressure of the contrast on theocclusion device to mitigate the likelihood of damaging the occlusiondevice prior to deployment (see FIG. 1B-2). For instance, the distalmost opening 121′ can be positioned less than or equal to about 2.0inches from the distal end 114 or at a location that is between about1.5% and 2.5% of the working length of the catheter from the distal end114. The plurality of openings 121 can be positioned in a helicalconfiguration spanning less than or equal to about 0.5 inches measuredin an axial direction (e.g., about 0.3 inches, about 0.35 inches, orabout 0.4 inches). Further, the plurality of holes 121 can be equally,axially spaced apart (e.g., less than about 0.10 inches, such as about0.05 inches). In some embodiments, the contrast flow rate can be atleast about 2 cc/second or at least about 5 cc/second under an infusionpressure of no more than about 500 psi, preferably no more than about250 psi as measured under the Injection Protocol described herein. Forexample, the contrast flow rate can between about 2 cc/second and 5cc/second under infusion pressures between about 100 psi and 200 psi orbetween about 100 psi and 150 psi, such as about 2.0 or 2.3 cc/min.Additionally, the openings 121 provide a sufficient flow rate to preventthe buildup of pressure distal to the openings 121 such that theocclusion device is not inadvertently deployed simply by injectingcontrast. The flow rate through the openings 121 prevents a distalpressure higher than 50 psi when a 200 psi infusion pressure is appliedor a distal pressure of no more than 10 psi.

FIGS. 1B-3 and 1B-4 illustrate a possible embodiment of the innercatheter 120. The inner catheter 120 can include manifold 126 thatprovides access to a lumen of the inner catheter 120. Further, the innercatheter 120 can include a pusher member 123. When the delivery systemis assembled, the occlusion device can be positioned between the distalend 124 and the pusher member 123 of the inner catheter 120. The pushermember 123 can be used to push the occlusion device out of the outercatheter 110. As shown in FIG. 1B-4, the inner catheter 120 can alsoinclude a radiopaque marker 125 disposed near the distal end 124 of theinner catheter 120, so the user can monitor placement of the occlusiondevice.

Interlock Assembly with Resilient Members

It can be clinically desirable to assess the performance of theocclusion device prior to releasing the occlusion device from thedelivery system 100. Thus, in some embodiments, as shown in FIGS. 1C-1to 1C-3, the delivery system 100 c (including one or more features ofthe delivery system 100) and the occlusion device 140 can include aninterlock assembly 150 that allows the occlusion device 140 to beresheathed or repositioned. The interlock assembly 150 can removablysecure the inner catheter 120 c to the occlusion device 140. In someexamples, the occlusion device 140 can resemble 1500 any of theocclusion devices described below.

The interlock assembly 150 can include one or more resilient members 152and a corresponding number of recesses 154 (e.g., channels or grooves).As shown in FIG. 1C-3, the interlock assembly 150 can include a firstresilient member 152 a and a second resilient member 152 b; however,more resilient members can be utilized (e.g., three or four). Theresilient members 152 can extend from one of a reduced diameter portion(e.g., a proximal end 142) of the occlusion device 140 or a distal endof the inner catheter 120 c, and the recesses 154 can be disposed on theother of the reduced diameter portion (e.g., the proximal end 142) ofthe occlusion device 140 or the distal portion 156 of the inner catheter120 c. When the recesses 154 are disposed on the distal portion 156 ofthe inner catheter 120 c, a diameter of the distal end portion 156 canbe greater than a remaining portion of the inner catheter 120 c and lessthan or equal to a diameter of the proximal end 142 of the occlusiondevice 140 (see FIG. 1C-1). For example, as shown in FIG. 1C-1, theresilient members 152 can extend proximally from a proximal end 142 ofthe occlusion device 140, and the recesses 154 can be disposed at thedistal end portion 156 of the inner catheter 120 c.

As shown in FIG. 1C-3, the resilient members 152 can be biased toward anoutward extending position. Further, the resilient members 152 can eachhave a Z-shape, such that a first end of a resilient member 152 isaxially displaced from a second end of the resilient member 152. Incertain variants, the resilient members 152 can have a T-shape, alollipop shape, a Christmas tree shape, or any other suitable shape,which provides at least a first interference surface for engaging with asecond complementary interference surface to releasably retain theocclusion device on the catheter.

Additionally, the shape of the recesses 154 can generally correspond tothe shape of the resilient members 152, such that when the resilientmembers 152 are constrained within the outer catheter 110 c, theresilient members 152 can engage the corresponding recesses 154.

The interlock assembly 150 maintains the inner catheter 120 c and theocclusion device 140 in a locked configuration (see FIG. 1C-1) until theresilient members 152 are pushed beyond the distal end 114 c of thecatheter body 110 c (see FIG. 1C-2). When the resilient members 152 arepushed beyond the distal end 114 c of the catheter 110 c, the resilientmembers 152 move back to the outward extending position, therebyreleasing the occlusion device 140 from the inner catheter 120 c (seeFIG. 1C-3). Advantageously, the interlock assembly 150 allows theocclusion device 140 to be resheathed and repositioned so long as theresilient members 152 do not extend beyond the distal end 114 c of thecatheter 110 c. Further, the interlock assembly 150 requires noadditional movable members for actuation, which has a number ofbenefits, including, but not limited to, a reduced profile deliverysystem, a more flexible delivery system, fewer components formanufacturing, and fewer steps during the procedure.

Threaded Interlock Assembly

FIGS. 1D-1 and 1D-2 illustrate another embodiment of an interlockassembly 170 that can be used with delivery system 100 d (including oneor more features of the delivery system 100). The interlock assembly 170can include a first threaded region 172 at a reduced diameter portion(e.g., a proximal portion 162) of an occlusion device 160 and a second,corresponding threaded region 174 at a distal portion 156 of the innercatheter 120 d. For example, as shown in FIG. 1D-2, the first threadedregion 172 can be disposed around an interior surface of the proximalportion 162 of the occlusion device 160, and the second region 174 canbe disposed around an exterior surface of the distal end portion 176. Anouter diameter of the distal portion 176 can be less than an interiordiameter of the proximal portion 162 of the occlusion device 160, suchthat the second threaded region 174 can threadably engage the firstthreaded region 172.

The interlock assembly 170 can maintain the inner catheter 120 d and theocclusion device 160 in a locked configuration (see FIG. 1D-2) until theinner catheter 120 d is rotated counterclockwise and unscrewed from theocclusion device 160. Advantageously, the interlock assembly 170 allowsthe occlusion device 160 to be resheathed and repositioned so long asthe inner catheter 120 d remains threadably engaged with the occlusiondevice 160. Further, the interlock assembly 170 requires no additionalmovable members for actuation, which has a number of benefits,including, but not limited to, a reduced profile delivery system, a moreflexible delivery system, fewer components for manufacturing, and fewersteps during the procedure.

Delivery System with Interlock Catheter

With reference to FIGS. 1E-1 to 1E-6, another illustrative embodiment ofa delivery system is shown. Portions of the delivery system 100 eresemble the delivery system 100 discussed above. Accordingly, numeralsused to identify features of the delivery system 100 include an “e” toidentify like features of the delivery system 100 e (e.g., the outercatheter 110 e can resemble the outer catheter 110).

As shown in FIG. 1E-1, the delivery system 100 e can include aninterlock catheter 101 e extending through the outer catheter 110 e. Theinterlock catheter 101 can include an outer pusher 188 e and an innerpusher 186 e (see FIGS. 1E-5 and 1E-6). Further, a hemostasis valve 103e can form a seal between the outer catheter 110 e and the interlockcatheter 101 e. For purposes of illustration, the delivery system 100 eis described in connection with the occlusion device 1500 (described infurther detail below); however, the delivery system 100 e can be usedwith other occlusion devices, such as the occlusion device 1500.

Additionally, the interlock catheter 100 e and the occlusion device 1500can include an interlock assembly 180 e. The interlock assembly 180 ecan include a key ring 182 e that can be secured to a distal portion ofthe outer pusher 188 e. As shown in FIG. 1E-2, an inner diameter of thekey ring 182 e can be greater than an outer diameter of the distalportion of the outer pusher 188 e, such that the key ring 182 e can besecured over the distal portion of the outer pusher 188 e. Further, oneor more locking tabs 183 e (e.g., two, three, or four) can extend from adistal end of the key ring 182 e. The locking tabs 183 e can be biasedinward toward the inner pusher 186 e. Additionally, as shown in FIG.1E-1, the locking tabs 183 e can have a generally lollipop shape.Although, in other embodiments, the locking tab 183 e can have aT-shape, Z-shape, Christmas Tree shape, or any other suitable shape.

The interlock assembly 180 e can also include a locking drum 184 e thatis coaxial with the outer pusher 188 e (see FIGS. 1E-5 and 1E-6). Thelocking drum 184 e can be secured to the inner pusher 186 e, and thusadvanceable relative to the outer pusher 188 e. To secure the interlockcatheter 101 e to the occlusion device 1500, the inner pusher 186 e isadvanced until the locking drum 184 e pushes the locking tabs 183 eoutward into a corresponding interlock feature 1518 on a reduceddiameter portion (e.g., a proximal collar 1516) of the occlusion device1500 (see FIGS. 1E-2 and 1E-5). In this locked configuration, theocclusion device 1500 can be advanced through the outer catheter 110 eusing the interlock catheter 101 e.

To release the occlusion device 1500 from the outer pusher 188 e, theinner pusher 186 e is advanced further until a proximal end of thelocking drum 184 e is distal to the locking tabs 183 e (see FIG. 1E-3).In this configuration, the locking tabs 183 e can return to the inwardextending position such that the occlusion device 1500 can be detachedfrom the outer pusher 188 e (see FIGS. 1E-4 and 1E-6). Advantageously,the interlock assembly 180 e allows the occlusion device 1500 to beresheathed and repositioned so long as the outer pusher 188 is securedto the occlusion device 1500.

Delivery System with Interlocking Attachment Member and ContrastInjection

FIGS. 2A to 2K illustrate a method of using another embodiment of adelivery system 200 having an interlocking attachment member 231 thatinterfaces with an occlusion device O. Portions of the delivery system200 resemble the delivery system 100 discussed above. Accordingly,numerals used to identify features of the delivery system 100 areincremented by a factor of “100” to identify like features of thedelivery system 200 (e.g., the outer catheter 210 can resemble the outercatheter 110).

Generally, the delivery system 200 can include an inner catheter 220adapted to advance an occlusion device O (e.g., an hourglass-shapedocclusion device as described below) through the outer catheter 210 andinto the target vessel (see FIG. 2A). The inner catheter 220 can includean interlocking attachment member 231 that enables the clinician toadvance and retract the occlusion device O, so long as the proximal endof the occlusion device O remains constrained within the outer catheter210 and interfaces within the interlocking attachment member 231 (seeFIGS. 2L and 2M). When the proximal end of the occlusion device O isadvanced distally of the distal end 214 of the outer catheter 210, theproximal end of the occlusion device O expands and releases from theinterlocking attachment member 231 (see FIG. 2G). Advantageously, theinterlocking attachment member 231 enables the clinician to assess theperformance of the occlusion device O prior to releasing the occlusiondevice O from the delivery system 200.

FIGS. 2A and 2B illustrates a fully assembled delivery system 200 withthe inner catheter 220 extending through the outer catheter 210. Tobegin deployment, the distal lobe of the occlusion device D can bedeployed. The occlusion device O can be deployed by advancing the innercatheter 220 relative to the outer catheter 210 (see FIGS. 2C and 2D).With only the distal lobe of the occlusion device D deployed, contrastinjection can be delivered to confirm the position of the occlusiondevice O. Since the distal lobe of the occlusion device D is uncovered(e.g., bare metal struts), the occlusion device O does not occlude flowof the dye. As shown in FIGS. 2CC and 2DD, as the inner catheter 220 isadvanced, a distal face of the interlock attachment member 231interfaces with the occlusion device O at a location distal to theproximal end of the occlusion device O, such that the interlockattachment member 231 urges the occlusion device O in a distaldirection.

If the distal lobe D is improperly positioned, the inner catheter 220can be retracted to retract the occlusion device O (see FIG. 2E). Asshown in FIG. 2EE, as the inner catheter is retracted, a proximal faceof the interlock attachment member 231 interfaces with the occlusiondevice O (e.g., proximal hooks of the occlusion device O), such that theinterlock attachment 231 urges the occlusion device O in a proximaldirection.

Once the distal lobe 1202 e of the occlusion device 1200 e is properlyposition, the remaining portion of the occlusion device can be deployed(see FIGS. 2F and 2G). Next, the inner catheter 220 can be retractedrelative to the outer catheter 210 (see Figure H). As shown in FIG. 2HH,a proximal face of the ramp 229 is larger than an end portion E of thetubular membrane portion of the occlusion device T (e.g., a largerdiameter or larger surface area). Consequently, as the inner catheter220 is further withdrawn, the ramp 229 forces the tubular portion T toinvert (see FIGS. 2I and 2II), such that a proximal portion of thetubular membrane portion T that is within the proximal lobe P begins tofold over a remaining portion of the tubular membrane portion T. Viewedanother way, an inner surface of the tubular portion T becomes anexternal surface of the tubular portion T. During the inversion process,the tubular portion T moves from being positioned within the distal lobeD (see FIGS. 2H and 2HH) to being positioned within the proximal lobe P(see FIGS. 2J and 2JJ). Viewed another way, the tubular portion T movesfrom being external to a membrane cover M (see FIGS. 2H and 2HH) tobeing positioned within the membrane cover M (see FIGS. 2J and 2JJ).When the inner catheter 220 is fully removed from the occlusion device O(see FIG. 2K), the tubular portion T closes like a valve to preventblood from flowing through the tubular portion T. The tubular portion Thas sufficiently low collapse resistance such that when the deliverysystem 200′ (and guidewire, if present) is removed, the tubular portionT collapses (e.g., kinks, folds, buckles, flops over, or likewise) intoa closed position (see FIG. 12G).

FIGS. 2L to 2N illustrate the outer catheter 210 of the delivery system200. The outer catheter 200 permits contrast dye to be injected throughthe delivery system 200 and can be used to determine the position of theocclusion device before detaching the occlusion device from the deliverysystem 200.

The outer catheter 210 can have a working length of about 120 cm or anyother suitable working length described above. An internal diameter ofthe outer catheter 210 can be less than or equal to about 0.10 inches,such as about 0.05 inches. A distal portion of the outer catheter 210can be bulbous shaped if a marker band 225 is embedded within the outercatheter 210 (see FIG. 2N). As shown in FIG. 2N, the outer catheter 210can include at least three concentric layers, e.g., an inner layer 210′,an intermediate layer 210″, and an outer layer 210′″. The outer layer210′″ can be constructed from Pebax or other medical grade polymermaterials. The intermediate layer 210″ can be a stainless steel braid toreinforce the outer catheter 210. The inner layer 210′ can beconstructed from PTFE or other suitable medical grade polymer materials.If present, the radiopaque marker 225 can be embedded radially betweenthe outer layer 210′ and the intermediate layer 210″.

The outer catheter 210 can include a plurality of openings 221 (e.g., atleast two, five, six, eight, or more openings) disposed near a distalend 114 h of the outer catheter 210, such that contrast dye can bereleased near the proximal side of the occlusion device (see FIG. 2M).The placement of the openings 221 can remove the pressure of thecontrast on the occlusion device to mitigate the likelihood of damagingthe occlusion device prior to deployment. For instance, the distal mostopening 221′ can be positioned less than or equal to about 2.0 inchesfrom the distal end 114 h or at a location that is between about 1.5%and 2.5% of the working length from the distal end 114 h. The pluralityof openings 221 can be positioned in a helical configuration spanningless than or equal to about 0.5 inches measured in an axial direction(e.g., about 0.3 inches, about 0.35 inches, or about 0.4 inches).Further, the plurality of holes 221 can be equally, axially spaced apart(e.g., less than about 0.10 inches, such as about 0.05 inches). Thecontrast flow rate can be at least about 2 cc/second or at least about 5cc/second under an infusion pressure of no more than about 500 psi,preferably no more than about 250 psi as measured under the InjectionProtocol described herein. For example, the contrast flow rate canbetween about 2 cc/second and 5 cc/second under infusion pressuresbetween about 100 psi and 200 psi or between about 100 psi and 150 psi,such as about 2.0 or 2.3 cc/min. Additionally, the openings 221 providea sufficient flow rate to prevent the buildup of pressure distal to theopenings 221 such that the occlusion device is not inadvertentlydeployed simply by injecting contrast. The flow rate through theopenings 221 prevents a distal pressure higher than 50 psi when a 200psi infusion pressure is applied or a distal pressure of no more than 10psi.

FIGS. 2O and 2P illustrate the inner catheter 220 of the delivery system200. The inner tubular body 220 has a proximal end 222 and a distal end224. A proximal hub 226 can be positioned at the proximal end 222 of theinner catheter 220 to provide access to a lumen of the inner catheter220. A pusher tip 227 can be positioned at the distal end 224 of theinner catheter 220. The pusher tip 227 can be tapered at a distal and/ora proximal portion of the pusher tip 227, with a uniform diametersection therebetween. If the pusher tip 227 and the inner catheter 220are separate components, a radiopaque marker 225 can be positionedradially between the pusher tip 227 and the inner catheter 220.

As shown in FIG. 2P, a distal ramp 229 can be positioned proximal to thepusher tip 227. The distal ramp 229 can be tapered in a distaldirection. As explained in further detail below, when the deliverysystem 200 is used with an hourglass-shaped occlusion device having atubular membrane portion (as described below), the ramp 229 can invert atubular section of an occlusion membrane as the inner catheter 220 isretracted through the occlusion device.

As mentioned above, the delivery system 200 can include an interlockingattachment member 231 positioned proximal to the distal ramp 229. Asshown in FIG. 2P, the interlocking attachment member 231 can bering-shaped. The interlocking attachment member 231 can interface withan occlusion device having proximal hooks, barbs, or the like (see e.g.,occlusion device 1200 e). The proximal hooks of the occlusion device caninterface with the interlocking attachment member 231 so long as theproximal end of the occlusion device remains constrained within theouter catheter 210. The outer catheter 210 constrains the proximal endof the occlusion device, thereby allowing the occlusion device tointerface with the interlocking attachment member 231.

The length of the proximal hooks of the occlusion device and the lengthof the interlocking attachment member 231 can be optimized to provide acontrolled amount of axial clearance in between proximal hooks of theocclusion device and the interlocking attachment member 231 (see FIGS.2DD and 2EE). When the inner catheter 220 advances the occlusion devicedistally, the interlocking attachment member 231 pushes on a portion ofthe occlusion device distal to the proximal end of the occlusion devicebut does not engage the proximal hooks of the occlusion device (see FIG.2DD). The axial clearance enables the proximal end of the occlusiondevice to expand when advanced out of the outer catheter 210. Prior tothe proximal end of the occlusion device being advanced distally of thedistal end of the outer catheter 210, retracting the inner catheter 220causes the interlocking attachment member 231 to engage the proximalhooks and retract the occlusion device (see FIG. 2EE).

As shown in FIG. 2P, a proximal coupler 233 can be positioned proximalto the interlocking attachment member 231. The proximal coupler 233 canbe tapered in a proximal direction. The proximal coupler 233 can preventthe occlusion device from moving proximally prior to deployment.

FIGS. 2Q and 2R illustrate another delivery system 200′. Portions of thedelivery system 200′ resemble the delivery system 200 discussed above.Accordingly, numerals used to identify features of the delivery system200 are include an apostrophe (′) to identify like features of thedelivery system 200′ (e.g., the outer catheter 210′ can resemble theouter catheter 210).

The interlock attachment member 231′ can have a number of longitudinallyextending grooves 240′ (indentations, openings, or the like)circumferentially positioned around the interlock attachment member231′. These grooves 240′ are shaped to receive a neck portion 244′ of amarker 242′ (see FIG. 2Q).

As shown in FIG. 2R, at least a proximal lobe P of the occlusion deviceO can include a number of markers 242′. Each of these markers 242′ caninclude an aperture 246′ (eyelet, opening, or the like) and a neckportion 244′. These markers 242′ can be press-fit onto the strut endingsof the proximal lobe P. The markers 242′ can be radiopaque to facilitatevisualization of the occlusion device O.

The method of delivering the occlusion device O is similar to the methoddescribed in FIGS. 2A to 2K. Prior to full release (see FIG. 2Q), theocclusion device O can be retracted and repositioned. The occlusiondevice O is configured to interface with the interlock attachment member231′ until a proximal end of the occlusion device O has been releasedfrom the delivery system 200′ (see FIG. 2R).

Occlusion Device

The occlusion devices described herein can include an expandablestructure configured to move between an unexpanded or constrainedconfiguration and an expanded or unconstrained or enlargedconfiguration. The expandable structure can include any of a number ofmedical grade materials, including, but not limited to, polymers (e.g.,PET) or non-ferrous metals (e.g., nitinol, stainless steel, or cobaltchrome).

The expansion ratio of the expandable structure should be sufficientlylarge such that the occlusion device is capable of compressing to aminimum size suitable for delivery through a catheter having an outerdiameter of 6 F (i.e., 2.0 mm) or less, thereby minimizing trauma to thevessel during delivery. Further, the expansion ratio should besufficiently large such that a single, expanded occlusion device iscapable of preventing substantially all fluid from flowing past theocclusion device in vessel range of different sized target vessels.Although, additional occlusion devices (e.g., two or three) can bedelivered depending on clinical judgment.

The expandable structure can be configured to include an expansion ratiothat is at least about 3:1, at least about 5:1, preferably at leastabout 7:1, and more preferably at least about 8:1. In some examples, theexpansion ratio can be about 7:1 or about 8:1. In other words, adiameter of the expandable structure in the expanded configuration canbe at least about three times, at least about five times, preferably atleast about seven times, and more preferably at least about eight times,a diameter of the expandable structure in the unexpanded configuration.For example, the diameter of the expandable structure in the expandedconfiguration can be between about three times and about nine timesgreater, preferably at least about seven times greater, than thediameter of the expandable structure in the unexpanded configuration. Insome examples, the diameter of the expandable structure can be at leastabout seven times or about eight times greater than a diameter of theexpandable structure in the unexpanded configuration.

As described above, the delivery system preferably has a sufficientlysmall diameter to avoid causing damage to the vessel wall duringdelivery. Therefore, the occlusion device should be configured fordelivery through a catheter having an outer diameter that is less than 7F (2.3 mm), preferably less than 6 F (2.0 mm), for example 5F (1.67 mm),4 F (1.33 mm), or 3 F (1.0 mm). In the unexpanded configuration, theocclusion device can include an outer diameter that is less than orequal to about 2 mm or less than or equal to about 1.75 mm, preferablyless than or equal to about 1.5 mm. For example, the outer diameter ofthe occlusion device in the unexpanded configuration can be within about0.5 mm, or within about 0.25 mm, of about 1.25 mm. Further, a length ofthe occlusion device in the unexpanded configuration can be less than orequal to about 3 cm or less than or equal to about 2.5 cm, for example,within about 0.5 cm of about 2 cm.

As explained in further detail below, the expandable structure caninclude one or more strands braided to form the expandable structure.Each strand can include a diameter between about 0.025 mm and about 0.05mm. In the unexpanded configuration, the braided expandable structurecan include a pore size of no more than about 1.5 sq. mm, preferably nomore than about 1.25 sq. mm, for example, within about 0.25 sq. mm ofabout 1.0 sq. mm. Further, in the unexpanded configuration, the braidedstrands can form intersecting angles between about 70 degrees and about130 degrees, for example, between about 70 degrees and 90 degrees,between about 80 degrees and about 100 degrees, between about 90 degreesand about 110 degrees, between about 100 degrees and about 120 degrees,or between about 110 degrees and about 130 degrees.

An expanded diameter of the expandable structure can vary depending onthe application of the occlusion devices. For example, the diameter canvary depending on whether the occlusion device is delivered within arenal vessel, a cardiovascular vessel, a pulmonary vessel, aneurovascular vessel, or otherwise. In any of these vessels, theexpanded configuration must have an acceptable diameter, length, andradial outward forces to maintain proper vessel wall apposition andresist migration. In some implementations, the aspect ratio between theexpanded diameter and the expanded length can be less than or equal toabout 1:1, such as 1:2, or the length can be proportionally longerdepending on the desired application.

In the unconstrained expanded configuration, a maximum diameter of theocclusion device can be between about 1.0 to about 1.5 times or more adiameter of the target site in a vessel. In some applications, theocclusion device can expand to a diameter between about 5.0 mm and about11 mm, for example, within about 0.5 mm of each of about 6.0 mm, 7.0 mm,8.0 mm, 9.0 mm, or 10.0 mm. In some applications, the expanded diametercan be between about 4.0 mm and about 6.0 mm, for example, within about0.5 mm of about 4.5 mm. In other applications, the expanded diameter canbe between about 2.0 mm and about 3.0 mm, for example, within about 0.25mm of about 2.5 mm.

For example, in neurovascular applications, the expanded diameter can bebetween about 1.5 mm and about 4.0 mm, for example, within about 0.5 mmof each of about 2.0 mm, 2.5 mm, 3.0 mm, or 3.0 mm. Each of theseocclusion devices can be delivered through a catheter having an internaldiameter of less than or equal to about 0.7 mm (0.027″). The expansionratio can be at least about 5:1, for example, between about 5:1 and5.5:1 or between about 5.5:1 and about 6:1, such as about 5.8:1.

In some peripheral applications, the expanded diameter can be betweenabout 4.0 mm and about 6.0 mm, for example, within about 0.25 mm of eachof about 4.25 mm, 4.5 mm, 4.75 mm, 5.0 mm, 5.25 mm, 5.5 mm, or 5.75 mm.Each of these occlusion devices can be delivered through a catheterhaving an internal diameter of no more than about 1.0 mm (0.038″). Theexpansion ratio can be at least about 5:1, preferably at least about6:1, for example, between about 6:1 and about 7:1, such as about 6.2:1.

In other peripheral applications, the expanded diameter can be betweenabout 7.0 mm and about 12.0 mm, for example, within 0.5 mm of each ofabout 7.5 mm, 8.0 mm, 8.5 mm, 9.0 mm, 9.5 mm, 10.0 mm, 10.5 mm, 11.0 mm,or 11.5 mm. Each of these occlusion devices can be delivered through acatheter having an outer diameter of less than or equal to about 2.0 mm,for example, between about 1.5 mm and about 2.0 mm (e.g., 1.67 mm (5F)).

The expanded length should be between about 0.5 times and about 1.5times the diameter of the target vessel, or greater depending on thedesired performance. In some applications, the expanded length can bebetween about 2.5 mm to about 7.5 mm, for example, between about 4.0 mmto about 6.0 mm, or within about 0.5 mm of about 5.0 mm. In someapplications, the expanded length can be between about 2.0 mm to about6.0 mm, for example, between about 3.0 mm and about 5.0 mm, or withinabout 0.5 mm of about 4.5 mm. In some applications, the expanded lengthcan be between about 1.0 mm and about 3.0 mm, for example, within about0.5 mm of about 2.5 mm.

In some applications, the expanded lengths can vary from 1 cm to 5 cm(e.g., from 1 cm to 4 cm, from 2 cm to 5 cm, from 2 cm to 4 cm,overlapping ranges thereof, 1 cm, 1.5 cm, 2 cm. 2.5 cm, 3 cm, 3.5 cm, 4cm, 4.5 cm, 5 cm), and the expansion diameter can vary from 1 mm to 6 mm(e.g., from 1 mm to 4 mm, from 2 mm to 6 mm, from 3 mm to 5 mm,overlapping ranges thereof, 1 mm, 2 mm, 3 mm, 4 mm, 5 mm, 6 mm)depending on the vessel to be addressed. In some applications, theexpandable structure can be configured to expand to diameters largerthan 5 mm (e.g., 6 mm, 7 mm, 8 mm, 9 mm, 10 mm) or less than 2 mm (e.g.,1.8 mm, 1.6 mm, 1.4 mm, 1.2 mm, 1.0 mm).

As shown in at least FIGS. 7A to 10B, in some instances, one or bothends of the occlusion device can be tapered. A proximal end which tapersdown in diameter in the proximal direction can be useful to facilitateretraction. For example, an angle of a proximal tapered end can be lessthan or equal to about 45 degrees, for example, between about 15 degreesand about 30 degrees or between about 30 degrees and about 45 degrees.

Clinically, it can be desirable for the occlusion device to exertsufficient radial outward pressure to maintain proper vessel wallapposition and resist migration of the occlusion device afterdeployment. The occlusion device can have an average COP across adiameter between about 2.5 mm and about 8.0 mm (e.g., a diameter betweenabout 3.0 mm and about 8.0 mm) of between about 20 mmHg and about 250mmHg, such as between about 30 mmHg and about 140 mmHg, between about 30mm Hg and 80 mmHg, between about between about 70 mmHg and 100 mmHg,between about 90 mmHg and 120 mmHg, or between about 100 mmHg and 140mmHg. The occlusion devices described herein can exert a radial outwardpressure between about 30 mmHg and about 50 mmHg, for example, betweenabout 30 mmHg and about 40 mmHg, between about 35 mmHg and about 45mmHg, or between about 40 mmHg and about 50 mmHg at the diameter of anintended target site in a vessel. In some instances, a proximal end ofthe occlusion device can include features to cause radial outward forceto increase at the center of the occlusion device without traumatizingthe vessel. The radial outward force at the center of the occlusiondevice can increase by up to 20 mmHg, for example, between about 10 mmHgto about 15 mmHg, or between about 15 mmHg and about 20 mmHg.

The expandable structure should include a wall pattern configured tofacilitate proper vessel wall apposition and resist migration afterdelivery. At the same time, the wall pattern preferably permits theocclusion device to be collapsed inside the delivery system withoutnegatively impacting trackability and accurate deployment. In general,the wall pattern can include struts that run diagonal or perpendicularto blood flow to maintain proper vessel wall apposition and resistmigration. For example, the occlusion device can include a wall patternconfigured such that a backpressure generated from the blood flow canhelp stabilize the occlusion device without causing trauma to the vesselwall. In some instances, the wall pattern can be substantially uniformalong an entire length of the expandable structure. In some instances,the wall pattern can vary between the first and second end portions andthe middle portion. In some instances, the density of the wall patterncan vary across the length of the occlusion device, for example, thepore size of the occlusion device can gradually increase across thelength of the occlusion device or towards both ends from the center.

In any of these wall patterns, the pore size should be sufficientlylarge to maintain proper vessel wall apposition and resist migration.For example, the expanded average pore size can be greater than or equalto about 0.75 sq. mm, for example, within about 0.25 sq. mm of about 1.0sq. mm, within about 0.5 sq. mm of about 1.25 sq. mm, or within about0.5 sq. mm. of about 4.5 sq. mm.

Other methods for reducing migration can include incorporating one ormore anchors, such as barbs, hooks, or likewise, along any portion ofthe occlusion device, preferably an uncovered bare strut portion, suchas the middle portion or one of two end lobes of the occlusion device.

As another example, if the occlusion device is braided, the occlusiondevice can include one or more exposed strands or strand ends. Thebraided occlusion device can include one or more strands each havingstrand ends. At least some of those strand ends can remain exposed andcan be configured to anchor the occlusion device to the vessel wall. Inother words, at least some of the strand ends can be secured to anotherof the strand ends, looped backed and secured to the same strand, orotherwise transformed to an atraumatic end, while at least some other ofthe strand ends can remain unsecured and can be configured to anchor theocclusion device to the vessel wall. These unsecured strand ends can bedisposed anywhere along the occlusion device, for example, at least atone of the first and second end portions.

It can also be desirable to encourage endothelial growth or theformation of blood clots to ensure the permanency of the occlusiondevice. For example, the occlusion device can be coated with a substanceto promote endothelial growth or the formation of clots. In someinstances, the occlusion device can be coated with a chemical sclerosingagent. In some instances, the occlusion device can be coated with aliquid embolic (e.g., cohesives (i.e., Onyx) or adhesives (i.e. n-BCA).

The occlusion device can be configured to occlude substantially allfluid flow through a vessel using a single occluder, although multipleocclusion devices can be delivered. Further, the single occluder can beconfigured to immediately occlude fluid flow through the vessel using asingle occluder (e.g., upon expansion). Substantial occlusion caninclude occluding at least about 80%, at least about 85%, at least about90%, at least about 95%, or at least about 98% of fluid flow through thevessel.

As described below, the occlusion device can include a cover at leastpartially covering the expandable structure. The cover can include acover material including, but not limited to, PTFE, PET, silicone,latex, TecoThane, nylon, PET, Carbothane (Bionate), fluoropolymers,SIBS, TecoFlex, Pellethane, Kynar, or PLGA.

The cover should be substantially impermeable to blood with abiostability for at least about two weeks. Preferably, the permeabilityis less than about 0.1 mL/sq. cm/min. In some instances, the cover caninclude a pore size of less than or equal to about 0.075 sq. mm. In someinstances, the cover has less than or equal to about 20 percent openarea, less than or equal to about 15 percent open area, or within about2 percent of each of about 10 percent, 12 percent, 14 percent, 16percent, or 18 percent. Further, the cover should include sufficientelasticity and lubricity to permit the occlusion device to be deployedin catheters having An outer diameter of less than or equal to about 6 F(2.0 mm) or less than or equal to about 5 F (1.67 mm) and expand to adiameter at least about 2.5 mm and/or less than or equal to about 8.0mm. In some instances, the cover can be electronically charged orchemically modified to promote thrombogenicity. However, the coveringmaterial may be coated with a material to inhibit thrombus formationtemporarily (i.e. hydrophilic coating) so that the device can beretracted and repositioned prior to final placement. In addition, thecover should have sufficient tensile strength to resist yielding,stretching, or breaking under at least normal blood pressures. Forexample, the cover should be able to withstand pressures of at leastabout 140 mmHg, preferably at least about 160 mmHg.

The length of the fibers creating the covering material allows theelongation of the covering material to far greater with less force(0.25-0.75×) than that of the native cover materials described above ofthe same thickness. The length of the fibers can be between about 5microns and about 25 microns, such as within about 5 microns of each ofabout 10 microns, 15 microns, or 20 microns, although greater lengthsmay be used depending on desired parameters. These lengths permit theelongate of the cover material to at least two times greater. In somecases, the elongation is between about two times greater and about fivetimes greater, for example, about three times greater or about fourtimes greater. This elongation occurs with less than or equal to about75 percent, less than or equal to about 50 percent, or even about 25percent of the force necessary for native cover materials describedabove having the same thickness (e.g., between about 10 and about 30microns).

It can be desirable for the cover to include a thickness that issufficiently large to resist perforation during and after delivery, butsufficiently thin to minimize the diameter of the occlusion device inthe unexpanded configuration and the diameter of the delivery device.Preferably, the thickness of the cover is less than or equal to about 30microns, for example, within about 5 microns of each of about 15microns, 20 microns, or 25 microns.

The cover can surround at least a portion of the expandable structure.The surrounded portion of the expandable structure should besufficiently large to prevent fluid from flowing past the occlusiondevice when the occlusion device is expanded in the vessel. For example,the cover can surround the entire circumference of a covered portion ofthe expandable structure. Further, the cover can surround the expandablestructure such that at least one end of the occlusion device issubstantially closed. As shown in FIGS. 9B and 9C, the cover may onlysurround one of the first or second end portions of the expandablestructure. In some instances, a length of the covered portion can bebetween about approximately 15 percent and about 35 percent of adiameter of the target vessel or the expanded occlusion device, forexample, approximately 25 percent of a diameter of the target vessel orthe expanded occlusion device. In other examples, as shown in at leastFIG. 7A, the cover can surround the first end portion and the second endportion of the expandable structure, but leave a middle portionuncovered. In yet other examples, as shown in at least FIG. 7B, thecover can surround substantially the entire expandable structure.

In some clinical scenarios, it can be more desirable to cover only aportion of the expandable structure, such that at least the middleportion remains uncovered. The exposed wall pattern of the expandablestructure can help maintain proper vessel wall apposition and resistmigration of the occlusion device.

The expandable structure can be coated with the cover using anelectrospinning process. Electrospinning refers generally to processesinvolving the expulsion of flowable material from one or more orifices,and the material forming fibers are subsequently deposited on acollector. Examples of flowable materials include dispersions,solutions, suspensions, liquids, molten or semi-molten material, andother fluid or semi-fluid materials. In some instances, the rotationalspinning processes are completed in the absence of an electric field.For example, electrospinning can include loading a polymer solution ordispersion, including any of the cover materials described herein, intoa cup or spinneret configured with orifices on the outside circumferenceof the spinneret. The spinneret is then rotated, causing (through acombination of centrifugal and hydrostatic forces, for example) theflowable material to be expelled from the orifices. The material maythen form a “jet” or “stream” extending from the orifice, with dragforces tending to cause the stream of material to elongate into a smalldiameter fiber. The fibers may then be deposited on a collectionapparatus. Further information regarding electrospinning can be found inU.S. Publication No. 2013/0190856, filed Mar. 13, 2013, and U.S.Publication No. 2013/0184810, filed Jan. 15, 2013, which are herebyincorporated by reference in their entirety.

To facilitate occlusion of the target vessel site, the occlusion devicein an over the wire embodiment should include a sufficiently smallresidual guide wire hole after deployment or a valve for occluding theguidewire opening. After full deployment, the occlusion device shouldinclude a residual guidewire hole having a diameter of less than orequal to about 0.25 mm. However, prior to deployment, the guide wirehole must be sufficiently large in both the unexpanded and expandedconfiguration to accommodate a standard guide wire having a diameter ofat least about 0.25 mm, preferably at least about 0.4 mm.

Any of the occlusion devices described herein can include a number ofradiopaque features that permit the fluoroscopic visualization of theocclusion device during one or more of delivery, deployment,post-deployment, and retraction. The marker bands can be positionedalong the expandable structure. The marker bands can have a thickness ofat least about 0.01 mm and a length of at least about 0.1 mm. Suitablemarker bands can be produced from any number of a variety of materials,including platinum, gold, tantalum, and tungsten/rhenium alloy.

Turning to the figures, FIGS. 3A-3F illustrate the delivery systemincluding any of the features of the delivery system 100 shown in FIGS.1A and 1B. The delivery system can be used to deliver the occlusiondevice 300. As shown in the figures, the occlusion device can include abraided expandable structure having a tulip shape (e.g., laser cut witha woven pattern or braided from a plurality of strands). In other words,a diameter of a first end portion 302 can be smaller than a diameter ofa second end portion 304. Further, a diameter of the middle portion 306can be greater than the diameter of the first end portion 302, butsmaller than the diameter of the second end portion 304. The diametercan gradually decrease from the second end portion 304 to the first endportion 302.

As shown in FIG. 3D, the occlusion device 300 can include a cover 308surrounding at least the first end portion 302. The cover 308 cansurround the entire circumference of the first end portion 302 and closethe first end such that fluid cannot flow through the first end portion302. In some instances, the cover 308 can surround at least 20 percentof a length of the expandable structure, for example, between about 20percent and about 40 percent or between about 30 percent and about 50percent of the length of the expandable structure. Although, in otherembodiments, the cover 308 can surround substantially the entireexpandable structure, leaving a second end opened or substantiallyclosed.

As shown in FIG. 3F, the occlusion device 300 can include a central hub310 for engaging the inner catheter 120 prior to delivery. If theocclusion device 300 is formed from a plurality of braided wire strands,the central hub can also be configured to secure the strand ends of thebraided wire strands. Although the occlusion device 300 is describedwith the central hub 310, a central hub 310 is not necessary, and theinner catheter 120 may carry the occlusion device 300 without thecentral hub 310. Further, if the occlusion device 300 is formed from aplurality of braided wire strands, the braided wire strands can beheat-treated to maintain the position of the heated strands, or thestrand ends can be secured to each other.

FIGS. 4A-4G illustrate the delivery system including any of the featuresof the delivery system 100 shown in FIGS. 1A and 1B. The delivery systemcan be used to deliver the occlusion device 400. As shown in thefigures, the occlusion device can include a braided expandable structurehaving a substantially cylindrical or barrel shape (e.g., laser cut witha woven pattern or braided from a plurality of strands). In other words,a diameter of a first end portion 402 can substantially the same as adiameter of a second end portion 404. In some instances, a diameter ofthe middle portion 406 can substantially the same as the diameters ofthe first end portion 402 and the second end portion 404. In otherinstances, a diameter of the middle portion 406 can be no more thanabout 25 percent larger, or no more than about 10 percent larger, thanthe diameters of the first and second end portions 402, 404.

The occlusion device 400 can include a diamond wall pattern across thelength of the occlusion device. As shown in FIG. 4D, the first andsecond end portions 402, 404 can include a different wall pattern thanthe middle portion 406. For example, the percentage of open area of thefirst and second end portions 402, 404 can be greater than thepercentage of open area of the middle portion 406. Although, in otherexamples, the wall pattern can be substantially the same across a lengthof the occlusion device 400.

The first and second ends can each include a diamond pattern. Further,each end can include an inner band 412 of strand portions and an outerband 414 of strand portions. Each band 412, 414 can form the same numberof apexes and form a diamond pattern therebetween. The inner band 412can define a guide wire opening 416 at the center of the inner band 412,through which a guide wire can pass.

The occlusion device 400 can include a cover surrounding at least one ofthe first and second end portions 402, 404. The cover can surround theentire circumference of the first end portion 402 and/or second endportion 404 and substantially close the first and/or second ends suchthat fluid cannot flow through the covered end(s). In some instances,the cover can surround substantially the entire occlusion device 400. Asshown in FIG. 4G, the cover portion 408 a can surround the first endportion 402 and the cover portion 408 b can cover the second end portion404, thereby substantially closing both the first and second ends. Insome instances, each cover portion 408 a, 408 b can surround at least 20percent of a length of the occlusion device 400, for example, betweenabout 20 percent and about 40 percent or between about 30 percent andabout 50 percent.

FIGS. 5A-5G illustrate the delivery system including any of the featuresof the delivery system 100 shown in FIGS. 1A and 1B. The delivery systemcan be used to deliver the occlusion device 500. As shown in thefigures, the occlusion device can include a braided expandable structurehaving a substantially cylindrical or barrel shape (e.g., laser cut witha woven pattern or braided from a plurality of strands). In other words,a diameter of a first end portion 502 can be substantially the same as adiameter of a second end portion 504. In some instances, a diameter ofthe middle portion 506 can substantially the same as the diameter of thefirst end portion 502 the second end portion 504. In other instances, adiameter of the middle portion 506 can be no more than about 25 percentlarger, or no more than about 10 percent larger, than the diameters ofthe first and second end portions 502, 504.

Similar to the occlusion device 400, the occlusion device 500 caninclude a diamond wall pattern across the length of the occlusiondevice. As shown in FIG. 5D, the wall pattern can be substantially thesame across a length of the occlusion device 500. However, in otherexamples, the first and second end portions 502, 504 can include adifferent wall pattern than the middle portion 506. For example, thepercentage of open area of the first and second end portions 502, 504can be greater than the percentage of open area of the middle portion506.

The first and second ends can each include a diamond pattern. As shownin FIGS. 5F and 5G, each end can include a band 518 of circumferentiallydisposed diamonds. The band 518 can define a guide wire hole 516 at thecenter of the inner band, through which a guide wire can pass.

The occlusion device 500 can include a cover surrounding at least one ofthe first and second end portions 502, 504. The cover can surround theentire circumference of the first end portion 502 and/or second endportion 504 and substantially close the first and/or second ends suchthat fluid cannot flow through the covered end(s). In some instances,the cover can surround substantially the entire occlusion device 400. Asshown in FIG. 5G, the cover portion 508 a can surround the first endportion 502, and the cover portion 508 b can cover the second endportion 504, thereby substantially closing both the first and secondends. In some instances, each cover portion 508 a, 508 b can surround atleast 20 percent of a length of the expandable structure, for example,between about 20 percent and about 40 percent or between about 30percent and about 50 percent.

FIG. 6 illustrates an occlusion device 600 having a braided expandablestructure (e.g., laser cut with a woven pattern or braided from aplurality of strands). The expandable structure can include asubstantially hourglass shape. In other words, a diameter of a first endportion 602 can be substantially the same as a diameter of a second endportion 604. Further, a diameter of the middle portion 606 can besubstantially smaller than the diameters of the first and second endportions 602, 604. In some instances, the diameter of the middle portion606 can be at least about 50 percent, at least about 60 percent, atleast about 70 percent, at least about 80 percent, or at least about 90percent smaller than the diameters of the first and second end portions602, 604. The middle portion 606 can define a guide wire passage largeenough for a conventional guide wire to pass.

The occlusion device 600 can include a cover surrounding the outsidesurface or the inside surface on at least one of the first and secondlobes or end portions 602, 604. The cover can surround the entirecircumference of the first end portion 602 and/or second end portion604. In some instances, the cover can surround substantially the entireocclusion device 600. As shown in FIG. 6, the cover 608 can surround thesecond end portion 604. In some instances, each cover 608 can surroundat least 25 percent of a length of the expandable structure, forexample, between about 40 percent and about 60 percent of the length ofthe expandable structure, such as about 50 percent of the length of theexpandable structure.

FIGS. 7A-7B illustrate the occlusion device 700. As shown in thefigures, the occlusion device 700 can include a braided, elongateexpandable structure (e.g., laser cut with a woven pattern or braidedfrom a plurality of strands). As shown in the figures, the expandablestructure can define a diamond wall pattern along a length of theexpandable structure. Further, the expandable structure can includetapered first and second end portions 702, 704. The first and second endportions 702, 704 can each define a guide wire hole large enough topermit a conventional guide wire to pass through the occlusion device.

A diameter of a middle portion 706 can be greater than a diameter of afirst end portion 702 and a diameter of a second end portion 704. Thediameter of the middle portion 706 can be no more than about 60 percent,50 percent, or 40 percent larger than the diameters of the first andsecond end portions 702, 704. In some instances, the middle portion 706can be at least as long as the first and second end portions 702, 704combined.

The occlusion device 700 can include a cover surrounding at least one ofthe first and second end portions 702, 704. The cover can surround theentire circumference of the first end portion 702 and/or second endportion 704 and substantially close the first and/or second ends suchthat fluid cannot flow through the covered end(s). As shown in FIG. 7A,the cover portion 708 a can surround the first end portion 702, and thecover portion 708 b can cover the second end portion 704, therebysubstantially closing both the first and second ends. In some instances,each cover portion 708 a, 708 b can surround at least 10 percent of alength of the expandable structure, for example, between about 10percent and about 20 percent or between about 20 percent and about 30percent. In some instances, as shown in FIG. 7B, the cover 708 c cansurround substantially the entire occlusion device 700.

FIG. 8 illustrates an occlusion device 800 formed from one or morestrands woven to form an expandable structure. The expandable structurecan include a first portion 802, a second portion 804, and a middleportion 806 therebetween. The first and second end portions 802, 804 caninclude tapered ends. Further, the first and second end portions 802,804 can each include a smallest diameter that is at least large enoughto permit a conventional guide wire to pass through.

The middle portion 806 can include a diameter that is substantiallylarger than a diameter of the first and second end portions 802, 804.For example, the diameter of the middle portion 806 can be at leastabout 50 percent or at least about 75 percent larger than a diameter ofthe first and second end portions 802, 804. In some instances, thediameter of the middle portion 806 can be between about 60 percent and80 percent larger or between about 70 percent and about 90 percentlarger. Further, as shown in FIG. 8, the middle portion 806 can includea non-uniform diameter; for example, the middle portion 806 can begenerally rounded to form a bulbous shape.

Although not shown, the occlusion device 800 can include a coversurrounding at least one of the first and second end portions 802, 804.The cover can surround the entire circumference of the first end portion802 and/or second end portion 804 and substantially close the firstand/or second ends such that fluid cannot flow through the coveredend(s). In some instances, each cover portion can surround at least 10percent of a length of the expandable structure, for example, betweenabout 10 percent and about 20 percent or between about 20 percent andabout 30 percent. In some instances, the cover can surroundsubstantially the entire occlusion device 800.

FIG. 9A illustrates an occlusion device 900 formed from one or morestrands woven to form an expandable structure. The expandable structurecan include a first portion 902, a second portion 904, and a middleportion 906 therebetween. The first and second end portions 902, 904 caninclude tapered ends. Further, the first and second end portions 902,904 each include a smallest diameter that is at least large enough topermit a conventional guide wire to pass through.

The middle portion 906 can include a diameter that is substantiallylarger than a diameter of the first and second end portions 902, 904.For example, the diameter of the middle portion 906 can be at leastabout 50 percent, or at least about 75 percent larger than a diameter ofthe first and second end portions 902, 904. In some instances, thediameter of the middle portion 906 can be between about 60 percent and80 percent larger or between about 70 percent and about 90 percentlarger. Further, as shown in FIG. 9, the middle portion 906 can includea substantially uniform diameter.

The occlusion device 900 can include a cover 908 surrounding at leastone of the first and second end portions 902, 904. The cover 908 cansurround the entire circumference of the first end portion 902 and/orsecond end portion 904 and substantially close the first and/or secondends such that fluid cannot flow through the covered end(s). In someinstances, each cover portion can surround at least 10 percent of alength of the expandable structure, for example, between about 10percent and about 20 percent or between about 20 percent and about 30percent. As shown in the figures, the cover 908 surrounds the first endportion 902. However, in some instances, the cover can surround thesecond end portion 904 or substantially the entire occlusion device 900.

FIGS. 10A-10B illustrate the occlusion device 1000. As shown in thefigures, the expandable structures can define a diamond wall patternalong a length of the expandable structure. Further, the expandablestructure can include tapered first end portion 1002 and an openedsecond end portion 1004. Although the first end portion 1002 is tapered,the first end portion 1002 still defines a guide wire hole large enoughto permit a conventional guide wire to pass through the occlusiondevice. A diameter of a middle portion 1006 can be substantially thesame as a diameter of the second end portion 1004.

As shown in FIG. 10B, the occlusion device 1000 can include a cover 1008surrounding at least the first end portion 1002. The cover 1008 cansurround the entire circumference of the first end portion 1002 suchthat fluid cannot flow through the covered end. In some instances, thecover 1008 can surround at least 10 percent of a length of theexpandable structure, for example, between about 10 percent and about 20percent or between about 20 percent and about 30 percent. As shown inFIG. 10A, the cover 1008 can surround substantially the entireexpandable structure.

FIGS. 11A-11C illustrate another exemplary embodiment of an occlusiondevice 1100. As shown in the figures, the occlusion device 1000 caninclude a substantially uniform diameter. The occlusion device 1100 alsodefines a substantially uniform diamond wall pattern along a length ofthe occlusion device 1100.

As shown in FIG. 11C, the occlusion device 1100 can include a drumhead1120 disposed within the first end portion 1102. The drumhead 1120 canbe configured to close the first end 1102 such that fluid is preventedfrom flowing through the occlusion device 1100.

Further, the occlusion device 1100 can include a cover 1108 surroundingat least a portion of the occlusion device 1100. For instance, the cover1108 can cover the drumhead 1120, or, as shown in FIGS. 11A-11C, thecover 1108 can surround at least the middle portion 1106 and the secondend portion 1104. Although, depending on the desired performance of thecover 1108, the cover 1108 can extend along different lengths of theocclusion device. In some scenarios, it may be desirable to have greateroverlap between the cover 1108 and the frame to adequately anchor thecover 1108 to the frame. For example, the cover 1108 can extend along atleast about 50 percent, as at least about 60 percent, at least about 70percent, at least about 80 percent, or at least about 90 percent of thelength of the occlusion device 1100. In some examples, the cover 1108extends along substantially the entire length of the occlusion device1100. In other scenarios, it may be desirable to leave a higherpercentage of the frame uncovered to facilitate endothelization, forexample, across less than about 50 percent, less than about 40 percent,less than about 30 percent, or less than about 20 percent of the lengthof the occlusion device 1100. Preferably, to achieve bothendothelization and sufficient overlap, the cover 1108 should extendacross at least about 25 percent of the length of the frame and no morethan about 50 percent of the length of the frame, for example, withinabout 5 percent of each of about 30 percent, 35 percent, 40 percent, or45 percent.

Although certain embodiments have been described herein within respectto the illustrated expandable structures, the occlusion devicesdescribed herein can include differently shaped or differently formedexpandable structures. For example, the expandable structure can besubstantially conical, coiled, or any other conventional stent shape. Asanother example, the expandable structure can include a laser cut frame.In some instances, the frame can include a first closed end and a secondopened end. The percentage of open area of the second opened end can begreater than the percentage of open area of the first closed end.

The specific examples described above in connection with FIGS. 3A-11Care for illustrative purposes only and should not be construed aslimiting. Any combination of the configuration, shape, or wall patternof the expandable structure can be combined with any type or amount ofcovering described herein.

Further, any of the features of the occlusion devices (e.g., expansionratio, shapes, dimensions, materials, covers, etc.) disclosed herein canbe accomplished in a stent, having two open ends and a central lumen tomaintain vascular patency and permit perfusion.

Hourglass-Shaped Occlusion Device—Axially Asymmetrical in ConstrainedConfiguration

FIGS. 12A and 12F illustrate an occlusion device 1200 a having a firstlobe or end portion 1202 a, a second lobe or end portion 1204 a, and acentral or neck portion 1205 a extending between the first and secondend portions 1202 a, 1204 a. The first end portion 1202 a can generallyrefer to the distal end portion or the anchor portion of the occlusiondevice 1200 a and the second end portion 1204 a can generally refer tothe proximal end portion or the occlusive portion of the occlusiondevice 1200 a when the occlusion device 1200 a is introduced into thepatient. As described in further detail below, the second end portion1204 a can be coated such that the second end portion 1204 a providesocclusion, while the first end portion 1202 a maintains an open cellstructure to anchor the occlusion device 1200 a and permit lateral flow.Further, the open cell structure of the first end portion 1202 a enablesthe clinician to partially deploy the occlusion device 1200 a againstthe wall of the vessel (e.g., just the first end portion 1202 a) andconfirm the position of the occlusion device 1200 a by injectingcontrast (e.g., by using delivery system 200) without materiallyimpeding flow or raising hydrostatic pressure. In contrast, if amechanically occlusive element were partially deployed, the mechanicallyocclusive element would impede flow and raise hydrostatic pressure.

As shown in FIG. 12A, the diameter of the central portion 1205 a can beless than a diameter of the first or second end portions 1202 a, 1204 a,e.g., the occlusion device 1200 a can have a generally hourglass shape(see FIG. 12A). For example, the diameter D₁ of the central portion 1205a can be between about 5% and about 25% of the diameter D₂ of the firstor second end portions 1202 a, 1204 a, preferably less than or equal toabout 15%, or less than or equal to about 10% of the diameter D₂ of thefirst or second end portions 1202 a, 1504. The diameter of the hub(e.g., uncut hypotube portion 1205 a′) D₃ can be substantially equal tothe diameter of the proximal and distal lobes D₄ when in the collapsedconfiguration (see FIG. 12D). The diameter D₄ across the proximal anddistal lobes can be substantially the same in the collapsedconfiguration (see FIG. 12D).

The occlusion device 1200 a can be asymmetrical about a transverse axisT-T of the occlusion device 1200 a in the expanded and/or unexpandedconfigurations (see FIG. 12A). For example, in the expandedconfiguration, the occlusion device 1200 a can be asymmetrical about atransverse axis T-T.

As shown in FIG. 12A, a uniform portion 1204 a′ of the second endportion 1204 a can have a generally uniform diameter (e.g., cylindrical)and a tapered portion 1204 a″ of the second end portion 1204 a can tapertowards the central portion 1205 a. The tapered portion 1204 a″ of thesecond end portion 1204 a can form an angle α between about 45 degreesand about 75 degrees, between about 55 degrees and about 65 degrees,preferably about 60 degrees with respect to the longitudinal axis.

Similarly, a uniform portion 1202 a′ (e.g., cylindrical) of the firstend portion 1202 a can have a generally uniform diameter and a taperedportion 1202 a″ of the first end portion 1202 a can taper toward thecentral portion 1205 a. The tapered portion 1202 a″ of the first endportion 1202 a can form an angle β. Angle β can be substantially thesame as angle α.

Even if the angle of the tapered portions 1202 a″, 1204 a″ issubstantially the same, an angle γ can be different from an angle δrelative to the longitudinal axis. The angle γ can be measured from aline extending through a transition point T₁ (between the taperedportion 1204 a″ and the cylindrical portions 1204 a′) and the axialcenter C of the occlusion device 1200 a. The angle δ can be measuredfrom a line extending through a transition point T₂ (between the taperedportion 1202 a″ and the cylindrical portions 1202 a′) and the axialcenter C of the occlusion device 1200 a. Angle δ can be less than angleγ to reduce the force necessary to retract the first end portion 1202 ainto the delivery system.

As illustrated in FIG. 13F, each of the proximal (covered) 1204 e anddistal (typically bare strut) 1202 e lobes are connected to the centralhub 1205 e′ by a plurality of struts 1210 e which incline radiallyoutwardly in their respective directions away from the hub 1205 e′. Inthe illustrated embodiment, a shallower distal lobe strut 1280 e launchangle between the curved axis of the strut and the longitudinal axis ofthe implant is clinically desirable because it provides a ramped surfacethat facilitates easy resheathing of the deployed distal lobe of theimplant as it is pulled proximally back into the tubular deploymentcatheter. Preferably, the expanded implant is bilaterally asymmetrical,with the proximal struts 1282 e exhibiting a steeper launch angle fromthe hub. This enables the implant to reach the fully expanded diameterof the proximal lobe 1204 e over the shortest possible axial length.Thus, the shallow launch angle distal struts 1280 e and steeper launchangle proximal struts 1282 e optimize retrievability of the partiallydeployed implant while at the same time minimizes overall implantlength. As seen in FIG. 13B, the wall pattern of the implant may in oneembodiment exhibit bilateral symmetry in the collapsed configuration butexpands to demonstrate the bilateral asymmetry described above due to apreset shape in the Nitinol or other shape memory material of the frame.

The distal struts 1280 e are concave outwardly in a side elevationalview, defining a generally trumpet shaped or flared configuration. Thecurvature of the struts 1280 e as they leave the hub 1205 e′ and inclineradially outwardly do not necessarily have a constant radius ofcurvature, but can be considered to conform to a best fit circle Ahaving a constant radius (see FIG. 13F). The radius is generally atleast about 25%, in some embodiments at least about 30% or 35% or moreof the unconstrained diameter of the expanded distal lobe 1202 e. Forexample, in an implant having an unconstrained distal lobe diameter ofabout 10 mm, the radius is generally within the range of from about 2.5mm to about 5.5 mm, and in some embodiments between about 3 mm and 5 mm,or approximately 4 mm.

The proximal lobe struts 1282 e can have a steeper launch angle toenable the proximal lobe 1202 e to reach full diameter over a shortaxial distance from the hub. Thus, the radius of circle B which bestfits the launch geometry of the proximal struts is generally less thanabout 25%, preferably less than about 20% or 15% or less of the expandeddiameter of the proximal lobe 1202 e, depending upon the physicalproperties and dimensions of the strut material (see FIG. 13F).

The best fit circles A, B described above will preferably be locatedagainst the strut such that it is approximately symmetrical about themidpoint of the arc of the struts that define the concave outwardlyconcave curvature section. Thus, the midpoint of the arc in the distalstrut 1280 e illustrated in FIG. 13F is a greater radial distance fromthe longitudinal axis of the implant than is the midpoint of the arc inthe proximal strut 1282 e due to the proximal strut transitioning fromthe arc to a substantially linear shoulder which extends out to thegenerally cylindrical body of the proximal lobe.

As shown in FIG. 12A, a length L₁ of the second end portion 1204 a(including the tapered portion 1204 a″ and generally uniform portion1204 a′) can be greater than a length L₂ of the first end portion 1202 a(including the tapered portion 1202 a″ and generally uniform portion1202 a′). For example, L₂ can be between about 25% and about 75% of L₁,such as between about 50% and about 60%. Forces directed at a concavesurface of the second end portion 1204 a can provide a radially outwarddirected force to push the second end portion 1204 a open and increaseradial outward forces acting on the occlusion device 1200 a and thevessel wall, when the occlusive concave side is facing an upstreamdirection with respect to blood flow in the vessel. The occlusive lobe(e.g., the second end portion 1204 a) also places the hub under axialcompression, which increases the radial force on the bare metal strutlobe (e.g., the first end portion 1202 a). In certain aspects, thelength of the second end portion L₁ can be about the same as a diameterof the second end portion 1204 a. This ensures that the second endportion 1204 a does not rotate perpendicular to an axis of the vesseland ensures that other anti-migration features remain properly alignedand positioned.

A length L₃ of the uniform portion 1204 a′ of the second end portion1204 a can be longer than a length L₄ of the uniform portion 1202 a′ ofthe first end portion 1202 a′ (see FIG. 12A). For example, in theunconstrained configuration, the uniform portion 1204 a′ can include agreater number of circumferential rings R1, R2, R3 of open cells 1212 athan the uniform portion 1202 a′. For example, the uniform portion 1204a′ can include three circumferential rings R1, R2, R3 of open cells 1212a, while the uniform portion 1202 a′ can include one circumferentialring R4 of open cells 1212 a. A size of an open cell 1212 a incircumferential ring R1 can be substantially the same size as the sizeof an open cell 1212 a in circumferential ring R4. In the constrainedconfiguration, the second end portion 1204 a can include a greaternumber of circumferential rings of struts than the first end portion.For example, the second end portion 1204 a can include sixcircumferential rings C1, C2, C3, C4, C5, C6, of struts 1210 a, whilethe first end portion 1202 a can include four circumferential rings C7,C8, C9, C10 of struts 1210 a.

The occlusion device 1200 a can have an aspect ratio less than or equalto about 2:1 (unconstrained length to unconstrained lobe diameter), suchas between about 1:1 and about 2:1 or between about 1.5:1 and about 2:1.An unconstrained length of the occlusion device 1200 a can be betweenabout 10 mm and about 25 mm, in some implementations from about 15 mm toabout 22 mm. The first end portion 1202 a having an unconstrained lengthof less than about 50% of a length of the occlusion device 1200 a (e.g.,when the unconstrained length is 20 mm, the length of the proximalportion is less than about 10 mm), less than about 40% of a length ofthe occlusion device 1200 a (e.g., when the unconstrained length is 20mm, the length of the proximal portion is less than about 8 mm), or lessthan about 30% of a length of the occlusion device 1200 a (e.g., whenthe unconstrained length is 20 mm, the length of the proximal portion isless than about 6 mm). An unconstrained expanded diameter of theocclusion device 1200 a can be between about 5 mm and about 15 mm, suchas about 10 mm.

The occlusion device 1200 a can include an expandable frame 1206 a and amembrane 1208 a carried by the expandable frame 1206 a (see FIG. 12F).The expandable frame 1206 a can define a lumen therethrough tofacilitate delivery of the occlusion device 1200 a over a guide wire(e.g., a 0.018-inch guidewire). Further, the expandable frame 1206 a canhave a wall thickness of less than or equal to about 0.003 inches, suchas about 0.002 inches.

As shown in FIG. 12D, the first end portions and the second end portions1202 a, 1204 a of the expandable frame 1206 a can include a plurality ofinterconnected struts 1210 a that can be laser cut from a Nitinolhypotube. At least a portion of the central portion 1205 a can be a barehypotube section 1205 a′ (e.g., uncut). The circumferential thickness ofthe struts 1210 a can generally increase from the ends of the occlusiondevice toward the central portion 1205 a. For example, as shown in FIG.12D, the struts 1210 a at the central portion 1205 a can have a greatercircumferential thickness than the struts 1210 a at the first and secondend portions 1202 a, 1204 a (e.g., struts 1280 a, 1282 a can be thickerthan the struts in circumferential rings C1 and C2). The ends of thestruts 1280 a, 1282 a that are adjoined to the central hub 1205 a′ arespaced apart, while the other ends of the struts 1280 a, 1282 a are eachadjoined to two struts in the adjacent circumferential rings C6, C7 (seeFIG. 12D). The struts in the central portion 1205 a are positioned suchthat the central portion 1205 a forms a star shape when viewed from anend of the occlusion device 1200 a (see FIG. 12H). The laser cut designcan help reduce foreshortening to less than or equal to about 20%.

As shown in FIG. 12C, the struts 1210 a can be at least partially curvedand form a plurality of generally rhombus-shaped open areas 1212 a. Thedistal and proximal ends of the rhombus-shaped open areas 1212 a canform an angle α between about 55 degrees and about 95 degrees, such asbetween about 55 degrees and 70 degrees or between about 70 degrees andabout 85 degrees (see FIG. 12C). In some embodiments, an angle betweenabout 85 degrees and about 95 degrees may be preferable to increase theexpansion ratio. In other embodiments, an angle between about 55 degreesand about 65 degrees may be preferable to reduce chronic outwardpressure (described in further detail below).

The open areas 1212 a can be generally smaller closer to the centralportion 1205 a compared to the ends of the occlusion device 1200 a.Additionally, portions of the expandable frame 1206 a on which hydraulicpressure would force the expandable frame 1206 a inward can be moreporous to prevent the occlusion device 1200 a from collapsing. Byleveraging the hydraulic blood pressure to create a radial outwardforce, the occlusion device 1200 a can be made smaller and lighter, thusallowing greater expansion ratios and smaller catheter French sizes.

FIG. 12D illustrates the occlusion device 1200 a in a collapsedconfiguration. The occlusion device 1200 a can include a number ofinterconnected circumferential rings C each having a plurality of struts1210 a. As shown in FIG. 12D, in an embodiment where the axial length ofeach of the circumferential rings is approximately equal, the first endportion 1202 a can include a fewer number of circumferential rings Cthan the second end portion 1204 a. For example, the first end portion1202 a can include two or three or four circumferential rings C7, C8,C9, C10, while the second end portion 1204 a can include five or six ormore circumferential rings C1, C2, C3, C4, C5, C6. Additionally, theocclusion device 1200 a can include a number of strut endings 1211 aextending from either end of the occlusion device 1200 a. As shown inFIG. 12E, the strut ending 1211 a can be generally tapered with abulbous shaped end 1209 a. The bulbous shaped end 1209 a can help retainmarker bands if present or be provided with an aperture to receive apress fit marker disc (e.g., lollipop shaped with an aperture) as isknown in the art (see FIGS. 2Q and 2R).

The expandable frame 1206 a can be at least partially covered by a thinmembrane 1208 a (e.g., between about 10 microns and about 30 micronsthick) (see FIG. 12F). The membrane 1208 a should be sufficiently thickto facilitate occlusion, while still minimizing the profile of thecollapsed occlusion device 1200 a. Possible materials for the membrane1208 a can include PTFE, PET, silicone, latex, TecoThane, nylon, PET,Carbothane (Bionate), fluoropolymers, SIBS, TecoFlex, Pellethane, Kynar,or PLGA.

The membrane 1208 a can be applied to the expandable frame 1206 a in amanner that encapsulates at least some of the struts 1210 a, such thatthe membrane 1208 a is present along either or both an interior surfaceand an exterior surface of the expandable frame 1206 a. Possible methodsof applying the membrane 1208 a are described in further detail below.

As shown in FIG. 12F, the membrane 1208 a can cover at least one end ofthe expandable frame 1206 a and extend across at least a partial lengthof the expandable frame 1206 a. In some embodiments, the membrane 1208 aat least coats a portion of the occlusion device 1200 a that is concaveto the direction of the blood flow, which can be more occlusive andresist more migration than occlusion devices that only coat a surfaceconvex to the direction of the blood flow or coat the entire occlusiondevice or coat the entire occlusion device. For example, the membrane1208 a can cover at least a portion of or the entire the second endportion 1204 a and the first end portion 1202 a can be a bare frame.When the bare first end portion 1202 a is deployed before the coveredsecond end portion 1204 a, the bare first end portion 1202 a can atleast partially anchor the occlusion device 1200 a in the vessel andallow visualization before deploying the covered second end portion 1204a, which facilitates precise placement of the occlusion device 1200 a.

When the covered second end portion 1204 a is upstream (i.e.,anatomically proximal) from the bare first end portion 1202 a, theincrease in arterial pressure at the second end portion 1204 a increasesthe radially outward forces directed toward the membrane 1208 a, whichhelps the occlusion device 1200 a resist migration. A higher bloodpressure difference between the proximal and distal ends of theocclusion device 1200 a will cause higher outward forces. Further, whenthe covered second end portion 1204 a is upstream from the bare firstend portion 1202 a, forward pressure from blood flow acts on the centralportion 1205 a. After the occlusion device 1200 a expands, forces actingon the central portion 1205 a cause the tapered portion 1202 a″ of thefirst end portion 1202 a (e.g., struts closer to or adjacent to thecentral portion 1205 a) to collapse (e.g., bend inward), which causesthe uniform portion 1202 a′ (e.g., struts closer to or at a distal endof the occlusion device) to move outward and further anchor the firstend portion 1202 a in the vessel.

Additionally, the membrane 1208 a can be positioned on portions of theexpandable frame 1206 a on which hydraulic pressure will force theexpandable frame 1206 a outward. In some embodiments, portions of theexpandable frame 1206 a where the hydraulic pressure would force theexpandable frame 1206 a inward are not coated.

The membrane 1208 a can extend to form a thin extended tubular sectionof coating 1250 a through which the guidewire (e.g., a 0.018″ guidewire)can be introduced (see FIGS. 12F and 12G). The thin tube 1250 a canextend through the first end portion 1202 a or the second end portion1204 a. As described in further detail below, the thin tube 1250 a canbe configured to invert from a position extending through the first endportion 1202 a such as during deployment to a position extending throughthe second end portion 1204 a following deployment. The thin tube 1250 acan extend across less than or equal to about 85% (e.g., between about75% and about 85%), less than or equal to about 75%, less than or equalto about 60%, or less than or equal to about 50% of the length of thesecond end portion 1204 a. In use, the thin tube 1250 a can havesufficiently low collapse resistance such that blood pressure will causethe thin tube 1250 a to collapse (e.g., kink, fold, buckle, flop over,or likewise) when the guidewire is removed (see FIG. 12H). The thin tube1250 a acts like a valve (e.g., a duckbill valve) to occlude theguidewire lumen 1252 a and aid in the capture and formation of clots.FIG. 12F illustrates a schematic cross-sectional view of the occlusiondevice 1200 a having the valve-like thin tube 1250 a. The tube 1250 amay be formed integrally with the formation of the membrane, during thespin coating process. Alternatively, the tube 1250 a may be separatelyformed and attached to the hub and/or membrane using suitable adhesives,solvent bonding, heat bonding, or other techniques known in the art.Alternatively, one, two, or more flaps or leaflets may be provided, toocclude the guidewire opening following removal of the guidewire,preferably on the upstream blood flow side of the hub.

After the occlusion device 1200 a has been deployed, the occlusiondevice 1200 a can resist migration (e.g., migrate less than about 5.0 mmfrom the deployed position, preferably less than about 4.0 mm, or lessthan about 2.0 mm) for at least 10 minutes under pressures of at leastabout 100 mmHg and/or less than or equal to about 300 mmHg, for example,between about 100 mmHg and 150 mmHg, between about 150 mmHg and about300 mmHg, between about 200 mmHg and about 300 mmHg, between about 250mmHg and about 300 mmHg, such as about 270 mmHg, as determined by theMigration Protocol described below.

In at least a straight 8 mm vessel or curved 8 mm vessel with a 20 mmradius to centerline of vessel, the structure of the deployed occlusiondevice 1200 a permits the device to resist migration under at leastaverage blood pressure (e.g., 120 mmHg) according to the MigrationProtocol described below. In at least a straight 8 mm vessel or curved 8mm vessel with a 20 mm radius to centerline of vessel, under retrogradevenous deployment conditions, the structure of the deployed occlusiondevice 1200 a permits the device to resist migration under at least 7mmHg of pressure according to the Migration Protocol described below.Migration is defined as continuous movement of the embolic device ormovement of the proximal end of the embolic device by greater than 5 mmfrom the initial location.

When the occlusion device 1200 a is deployed in the vessel, theocclusion device 1200 a can occlude at least about 80% of blood flowwithin 30 seconds, at least about 90% of blood flow within about 3minutes, and/or about 100% of blood flow within about five minutes,without reliance on biological processes. Because of the mechanicalmechanism of occlusion, performance is the same whether or not thepatient has been anticoagulated (e.g., heparin, aspirin, warfarin,Plavix, etc.). In some implementations, the occlusion device 1200 a canachieve complete occlusion within about two minutes or within about oneminute. Using the Occlusion Protocol described below, the occlusiondevice 1200 a can limit the flow rate through a vessel to no more thanabout 200 cc/min at 20 mmHg, such as to between about 50 cc/min andabout 150 cc/min, preferably less than about 130 cc/min, less than about100 cc/min at 20 mmHg or less than about 65 cc/min at 20 mmHg withinabout five minutes. Further, the occlusion device 1200 a can limit theflow rate through a vessel to no more than about 400 cc/min at 60 mmHgor no more than about 330 cc/min at 60 mmHg, such as to between about150 cc/min and about 250 cc/min, preferably less than or equal to about175 cc/min at 60 mmHg within about five minutes. The occlusion device1200 a can limit the flow rate through a vessel to about no more than600 cc/min at about 100 mmHg or 430 cc/min at 100 mmHg, such as tobetween about 200 mmHg and about 250 mmHg, preferably less than about225 cc/min at about 100 mmHg within about five minutes.

In at least a 3 mm curved vessel with a 7.5 mm radius to centerline ofvessel or a 8 mm vessel with a 20 mm radius to centerline of vessel,using the Occlusion Protocol described below, the occlusion device 1200a will permit a maximum flow rate of 130 cc/min at 20 mmHg (e.g., amaximum flow rate of 70 cc/min at 20 mmHg or 40 cc/min at 20 mmHg), 330cc/min at 60 mmHg (e.g., a maximum flow rate of 175 cc/min at 60 mmHg or125 cc/min at 60 mmHg), or 430 cc at 100 mmHg (e.g., a maximum flow rateof 315 cc/min at 100 mmHg or 185 cc/min at 100 mmHg) after about oneminute. In at least a 3 mm curved vessel with a 7.5 mm radius tocenterline of vessel or an 8 mm vessel with a 20 mm radius to centerlineof vessel, under retrograde venous deployment conditions, using theOcclusion Protocol described below, the occlusion device 1200 a willpermit a maximum flow rate of 130 cc/min at 20 mmHg after about oneminute.

The occlusion device 1200 a has an expansion ratio of at least about5:1. The expansion ratio of the occlusion device 1200 a allows theocclusion device 1200 a to treat different sized vessels between about2.5 mm and about 8.0 mm. For example, the same occlusion device 1200 athat can occlude a 2.5 mm vessel can occlude a 6.0 mm vessel.

The expansion ratio of the occlusion device 1200 a can be between about5:1 to about 10:1, such as at least about 5:1, at least about 6:1, atleast about 7:1, at least about 8:1, or at least about 9:1. In someimplementations, the expansion ratio can be at least about 10:1. Inother words, a diameter of the occlusion device 1200 a in the expandedconfiguration can be between about five times and about ten timesgreater than the diameter of the occlusion device 1200 a in theunexpanded configuration, such as at least about five times, at leastabout six times, at least about seven times, at least about eight times,or at least about nine times. In some implementations, the diameter ofthe expanded configuration can be at least about ten times greater thanthe diameter of the unexpanded configuration. The expansion ratio of theocclusion device 1200 a is sufficiently large such that the occlusiondevice 1200 a is capable of compressing to a minimum size suitable fordelivery through a catheter having a diameter of less than about 5 F,thereby minimizing trauma to the vessel during delivery. Further, theexpansion ratio of the occlusion device 1200 a is sufficiently largethat a single, expanded occlusion device is capable of preventingsubstantially all fluid from flowing past the occlusion device in thetarget vessel. Generally, the expansion ratio of each lobe is equal tothe ratio of the hub to the lobe in an unconstrained expansion.

A single occlusion device 1200 a can be used to treat a wide range ofvessel diameters. For example, the occlusion device 1200 a can have anexpansion range when delivered from a lumen having an internal diameterof at least about 2.0 mm up to at least about 8.0 mm or 10.0 mm or more,such as at least about 3.0 mm, at least about 4.0 mm, or at least about5.0 mm. For instance, a single occlusion device 1200 a can treat vesselshaving a diameter between about 2.5 mm and about 8.0 mm, or betweenabout 3.0 mm and 7.0 mm. Using a single occlusion device 1200 a to treata wide range of vessels can be desirable to reduce the total stock ofocclusion devices that must be kept on hand, and the ability to occludelarge vessels with a single occlusion device 1200 a can reduce costs.

Further, the single occlusion device 1200 a having an expansion range ofat least about 2.0 mm, 4.0 mm, or more, and also exhibits less than 20percent elongation when moving from the unexpanded configuration to theexpanded configuration, preferably less than about 15 percent.Minimizing elongation can help ensure accurate positioning of theocclusion device 1200 a.

In the expanded state, the occlusion device 1200 a can have anunconstrained diameter that is between about 30% and about 50% largerthan the vessel diameter. For vessels sized between about 2.0 mm andabout 8.5 mm in diameter, the diameter of the expanded occlusion device1200 a can be at least about 2.6 mm and/or less than or equal to about12.75 mm, e.g., between about 9 mm and about 11 mm, such as about 10 mm.

The occlusion device 1200 a may provide a chronic outward pressure(“COP”). As used herein, COP is the radial pressure (expressed in termsof mmHg) necessary to maintain stability of the occlusion device in avessel under normal physiological blood pressure (i.e., about 135 mmHg).Radial forces used to determine the following COP values were based ondata collected using the Migration Protocol described below. Further,the calculation of the COP assumes that the occlusion device 1200 aforms a complete seal, and thus the flow rate equals zero and shearforces equal zero. The calculation also assumes that the occlusiondevice 1200 a is rigid, and thus the normal force due to transfer ofhydraulic force to the vessel wall equals zero.

Using these assumptions, the occlusion device can provide a COP betweenabout 20 mmHg and about 250 mmHg, such as between about 30 mmHg andabout 140 mmHg, between about 30 mm Hg and 80 mmHg, between aboutbetween about 70 mmHg and 100 mmHg, between about 90 mmHg and 120 mmHg,or between about 100 mmHg and 140 mmHg., for vessels having a diameterbetween about 3 mm and about 8 mm under a physiological pressure ofabout 135 mmHg, preferably between about 20 N/mm² (2.67 kPa) and about50 N/mm² (6.67 kPa). For example, the occlusion device 1200 a canprovide about 48 mmHg (6.4 kPa) of radial pressure in a 7 mm vessel witha physiological pressure of about 135 mmHg pressure when the length ofthe contact area between an exemplary embodiment of the occlusion device1200 a and the vessel wall is about 12.5 mm (e.g., L₁=4.5 mm, L₂=8.0mm). The occlusion device 1200 a can provide about 20 mmHg (2.67 kPa) ofradial pressure in a 7 mm vessel with a physiological pressure of about135 mmHg pressure when the length of the contact area is about 30.0 mm,the entire length of an exemplary embodiment of the occlusion device1200 a. The latter calculation assumes that a thrombus will form andthat the occlusion device 1200 a will transfer radial force through thethrombus and across the entire length of the occlusion device 1200 a.

Hourglass-Shaped Occlusion Device—Axially Symmetrical in ConstrainedConfiguration

FIGS. 13A through 13E illustrate another hourglass-shaped occlusiondevice 1200 e having the same general structure and properties asocclusion device 1200 a. In generally, the occlusion device 1200 e isadapted to move between a constrained configuration (FIG. 13B) and anunconstrained configuration (FIG. 13A). The occlusion device 1200 e canhave any number of the characteristics (e.g., dimensions, construction,performance, etc.) as the occlusion device 1200 a except as describedbelow.

Similar to the occlusion device 1200 a, as shown in FIG. 13A, theocclusion device 1200 e can have a first lobe or end portion 1202 e, asecond lobe or end portion 1204 e, and a central or neck portion 1205 eextending between the first and second end portions 1202 e, 1204 e. Thefirst end portion 1202 e can generally refer to the distal end portionor the anchor portion of the occlusion device 1200 e and the second endportion 1204 e can generally refer to the proximal end portion or theocclusive portion of the occlusion device 1200 e when the occlusiondevice 1200 e is introduced into the patient. The second end portion1204 e can be coated such that the second end portion 1204 e providesocclusion, while the first end portion 1202 e maintains an open cellstructure to anchor the occlusion device 1200 e and permit lateral flow.Further, the open cell structure of the first end portion 1202 e enablesthe clinician to partially deploy the occlusion device 1200 e againstthe wall of the vessel (e.g., just the first end portion 1202 e) andconfirm the position of the occlusion device 1200 a by injectingcontrast (e.g., by using delivery system 200) without materiallyimpeding flow or raising hydrostatic pressure. In contrast, if amechanically occlusive element were partially deployed, the mechanicallyocclusive element would impede flow and raise hydrostatic pressure.

As shown in FIG. 13A, the diameter of the central portion 1205 e can beless than a diameter of the first or second end portions 1202 e, 1204 e,e.g., the occlusion device 1200 e can have a generally hourglass shape(see FIG. 13A). For example, the diameter D₁ of the central portion 1205e can be between about 5% and about 25% of the diameter D₂ of the firstor second end portions 1202 a, 1504, preferably less than or equal toabout 15%, or between about 10% and about 15% of the diameter D₂ of thefirst or second end portions 1202 e, 1204 e. The diameter of the hub canbe substantially equal to the diameter of the proximal and distal lobeswhen in the collapsed configuration.

As shown in FIG. 13A, the occlusion device 1200 e can be asymmetricalabout a transverse axis T-T of the occlusion device 1200 a in theexpanded. As shown in FIG. 13B, in an constrained position, the lengthL₁ of the first end portion 1202 e can be substantially the same as thelength L₂ of the second end portion 1204 e. For example, in theconstrained configuration, the second end portion 1204 e can include thesame number of circumferential rings as the first end portion, such assix rings C1, C2, C3, C4, C5, C6, of struts 1210 e (or four or five ormore) in the first end portion 1202 e and six rings C7, C8, C9, C10,C11, C12, of struts 1210 e (or four or five or more) in the second endportion 1204 e.

However, as shown in FIG. 13A, in the unconstrained position, the lengthL₃ of the generally uniform portion 1204 e′ of the second end portion1204 e can be less than the length L₄ of the generally uniform portion1202 e′ of the first end portion 1202 e. For example, L₃ can span abouttwo circumferential rings R₄, R₅ or less than three full circumferentialrings of open cells 1212 e, while L₄ can span about three fullcircumferential rings R1, R2, R3 of open cells 1212 e. Although thefirst end portion 1202 e and the second end portion 1204 e have the samelength in the unconstrained configuration, the first end portion 1202 eand the second end portion 1204 e to expand into differentconfigurations. A size of an open cell 1212 e in circumferential ring R1can be substantially the same size as the size of an open cell 1212 e incircumferential ring R4.

As shown in FIG. 13A, the angle α of the tapered portion 1204 a″ orangle β of the tapered portion 1202 a″ can be between about 45 degreesand about 75 degrees, between about 55 degrees and about 65 degrees,preferably about 60 degrees with respect to the longitudinal axis. Theangle α can be substantially the same as angle β.

However, even if the angle of the tapered portions 1202 e″, 1204 e″ issubstantially the same, an angle γ can be different from an angle δrelative to the longitudinal axis. The angle γ can be measured from aline extending through a transition point (between the tapered portion1204 e″ and the cylindrical portions 1204 e′) and the axial center ofthe occlusion device 1200 e. The angle δ can be measured from a lineextending through a transition point (between the tapered portion 1202e″ and the cylindrical portions 1202 a′) and the axial center of theocclusion device 1200 e. Angle δ can be less than angle γ to reduce theforce necessary to retract the first end portion 1202 e into thedelivery system.

During the manufacturing process, after the hypotube is laser cut, twodifferent sized mandrels are inserted into the occlusion device 1200 e.A first mandrel having a desired shape of the first end portion 1202 ecan be inserted through a distal end of the occlusion device 1200 e anda second mandrel having a desired shape of the second end portion 1204 ecan be inserted through a proximal end of the occlusion device 1200 e.The first mandrel can be locked together with the second mandrel. Withthe occlusion device 1200 e loaded on the first and second mandrels, theocclusion device 1200 e can be heat treated to the shape describedherein.

The occlusion device 1200 e can have an aspect ratio less than or equalto about 2:1 (unconstrained length to unconstrained lobe diameter), suchas between about 1:1 and about 2:1 or between about 1.5:1 and about 2:1.An unconstrained length of the occlusion device 1200 e can be betweenabout 10 mm and about 25 mm, in some implementations from about 15 mm toabout 22 mm. The first end portion 1202 e having an unconstrained lengthof less than about 50% of a length of the occlusion device 1200 e (e.g.,when the unconstrained length is 20 mm, the length of the proximalportion is less than about 10 mm), less than about 40% of a length ofthe occlusion device 1200 e (e.g., when the unconstrained length is 20mm, the length of the proximal portion is less than about 8 mm), or lessthan about 30% of a length of the occlusion device 1200 e (e.g., whenthe unconstrained length is 20 mm, the length of the proximal portion isless than about 6 mm). An unconstrained expanded diameter of theocclusion device 1200 e can be between about 5 mm and about 15 mm, suchas about 10 mm.

The occlusion device 1200 e can include an expandable frame 1206 e and amembrane 1208 e (not shown) carried by the expandable frame 1206 e (seeFIG. 13A). The expandable frame 1206 e can define a lumen G therethroughto facilitate delivery of the occlusion device 1200 e over a guide wire(e.g., a 0.018 inch guidewire) (see FIG. 13C). Further, the expandableframe 1206 e can have a wall thickness of less than or equal to about0.003 inches, such as about 0.002 inches.

As shown in 13B, the first end portions and the second end portions 1202e, 1204 e of the expandable frame 1206 e can include a plurality ofinterconnected struts 1210 e that can be laser cut from a Nitinolhypotube. At least a portion of the central portion 1205 e can be a barehypotube section 1205 e′ (e.g., uncut).

A length of each strut 1210 e can generally vary from an end of theocclusion device 1200 e toward the central portion 1205 e of theocclusion device 1200 e (see FIG. 13B). For example, a length of eachstrut 1210 e can generally increase from one or both ends of theocclusion device 1200 e to a central portion 1205 e of the occlusiondevice (e.g., from about 0.05 cm at the proximal and distal ends toabout 0.25 cm at the central portion 1205 e). For example, a length of astrut closest to the center can be about 150% of a length of a strutclosest to an end of the occlusion device 1200 e. For example, a lengthof a strut closest to the center of the occlusion device can be about0.09 inches and a length of a strut closest to an end of the occlusiondevice can be about 0.06 inches.

As an example, a first ring of struts R1 can have an axial length thatis about 115% of a length of a second, adjacent ring of struts R2. Forexample, a first ring of struts R1 can have an axial length of about0.0910 inches and a second ring of struts R2 can have an axial length ofabout 0.0785 inches. A second ring of struts R2 can have an axial lengththat is about 112% of a length of a third, adjacent ring of struts R3.For example, a second ring of struts R2 can have an axial length ofabout 0.0785 inches and a third ring of struts R3 can have an axiallength of about 0.0700 inches. A third ring of struts R3 can have anaxial length that is about 113% of a length of a fourth, adjacent ringof struts R4. For example, a third ring of struts R3 can have an axiallength of about 0.0700 inches and a second ring of struts R2 can have anaxial length of about 0.0620 inches. A fourth ring of struts R4 can havean axial length that is about the same as a fifth adjacent ring ofstruts R5. For example, a fourth ring of struts R4 and a fifth ring ofstruts R5 can have an axial length of about 0.0.0620 inches. A fifthring of struts R5 can have an axial length that is about 103% of alength of a sixth, adjacent ring of struts R6. For example, a fifth ringof struts R5 can have an axial length of about 0.0620 inches and a sixthring of struts R6 can have an axial length of about 0.06 inches.

A thickness in a circumferential direction of each strut 1210 e cangenerally vary from an end of the occlusion device 1200 e toward thecentral portion 1205 e of the occlusion device 1200 e. For example, athickness of each strut 1200 e can generally decrease from one or bothends of the occlusion device toward the central portion 1205 e of theocclusion device 1200 e. Varying the lengths and thicknesses of thestruts can evenly distribute force across the occlusion device 1200 e,which can decrease the chronic outward pressure the occlusion device1200 e exerts on the vessel or decrease the total length of theocclusion device 1200 e. As shown in FIG. 13B, in the constrainedconfiguration, a diameter of the occlusion device 1200 e can decreasefrom the ends of the occlusion device 1200 e toward the central portion1205 e of the occlusion device 1200 e. For example, there can be agradual decrease in diameter at an intermediate portion of the first endportion 1202 e and an intermediate portion of the second end portion1204 e. The intermediate portions can be positioned the same distancefrom a center of the occlusion device 1200 e. The intermediate portionscan extend across a same axial length of the occlusion device 1200 e.For example, each of the intermediate portions can extend across aboutless than 5 percent of an axial length of the entire length of theocclusion device 1200 e, such as about three percent. The intermediateportions can begin at a position about 20 percent to about 40 percent ofthe axial length from an end of the occlusion device, such as betweenabout 20 percent and about 30 percent or between about 30 percent andabout 40 percent. Although the profile of the occlusion device 1200 ecan be symmetrical in the constrained position, as described above, thefirst and second end portions 1202 e, 1204 e can expand into differentconfigurations (see FIG. 13A).

As shown in FIG. 13B, the struts in the circumferential rings C1 and C7(e.g., struts 1280 e, 1282 e) can be thicker than the struts incircumferential rings C6 and C12. Ends of the struts 1280 e, 1282 e thatare adjoined to the central hub 1205 e′ can be spaced apart, while theother ends of the struts 1280 e, 1282 e can be each adjoined to twostruts in the adjacent circumferential rings C2, C8 (see FIG. 13B). Thestruts 1280 e, 1282 e in circumferential rings C1 and C7 are positionedsuch that the central portion 1205 e forms a star shape when viewed froman end of the occlusion device 1200 e.

As shown in FIG. 13D, the strut endings 1211 e at the first end portion1202 e can be generally straight. FIG. 13E illustrates strut endings1215 e at the second end portion 1204 e of the occlusion device 1200 e.A length of each strut ending 1215 e can be between about 0.10 cm and0.20 cm. One or more of the strut endings 1215 e can have a hook 1217 efor interfacing with an interlock system described above.

When the occlusion device 1200 e is deployed using the delivery system200 (described above), the angle θ of the proximal hooks 1217 e of theocclusion device 1200 e can be optimized to maintain engagement betweenthe occlusion device 1200 e and the interlocking attachment member 231during retraction (described above) (see FIG. 13E). For example, theangle θ can be between about 60 degrees and about 90 degrees, such asabout 75 degrees.

When expanded, the ratio of strut width/thickness causes the struts andthe hooks to twist approximately 90 degrees. Twisting the hooks allowsfor a relatively “tall” hook while keeping the embolic strut thicknesslow to provide a greater profile for secure fixation.

Similar to the occlusion device 1200 a, the expandable frame 1206 e canbe at least partially covered by a thin membrane (partially removed toshow tubular section 1250 e) (e.g., between about 10 microns and about30 microns thick) (see FIG. 13A). The membrane should be sufficientlythick to facilitate occlusion, while still minimizing the profile of thecollapsed occlusion device 1200 e. Possible materials for the membranecan include PTFE, PET, silicone, latex, TecoThane, nylon, PET,Carbothane (Bionate), fluoropolymers (e.g., PVDF), SIBS, TecoFlex,Pellethane, Kynar, or PLGA.

As described below, the membrane (not shown) can be applied to theexpandable frame 1206 e in a manner that encapsulates at least some ofthe struts 1210 e, such that the membrane 1208 e is present along eitheror both an interior surface and an exterior surface of the expandableframe 1206 e. Possible methods of applying the membrane 1208 e aredescribed in further detail below.

The membrane can cover a portion of the occlusion device 1200 e that isconcave to the direction of the blood flow, which can be more occlusiveand resist more migration than occlusion devices that only coat asurface convex to the direction of the blood flow or coat the entireocclusion device or coat the entire occlusion device. For example, themembrane 1208 e can cover at least a portion of or the entire the secondend portion 1204 e and the first end portion 1202 e can be a bare frame.When the bare first end portion 1202 e is deployed before the coveredsecond end portion 1204 e, the bare first end portion 1202 e can atleast partially anchor the occlusion device 1200 e in the vessel andallow visualization before deploying the covered second end portion 1204e, which facilitates precise placement of the occlusion device 1200 e.

The membrane can extend to form a thin extended tubular section ofcoating 1250 e through which the guidewire (e.g., a 0.018″ guidewire)can be introduced (see FIG. 13A). The thin tube 1250 e acts like a valve(e.g., a duckbill valve) to occlude the guidewire lumen 1252 e and aidin the capture and formation of clots. An end portion 1251 e of the thintube 1250 e can have a reduced diameter compared to a remaining portionof the thin tube 1250 e to facilitate the closing of the valve. The thintube 1250 e can include a portion 1253 e that tapers toward the reduceddiameter end portion 1251 e.

The central portion 1205 e enables the occlusion device 1200 e to bendaround approximately a 90 degree bend at a vessel bifurcation accordingto the Trackability Protocol described below (e.g., in a simulated 3 mmvessel having a 7.5 mm radius to centerline of vessel or in a simulated8 mm vessel having a 20 mm radius to centerline of vessel). The centralportion 1205 e can include flexibility features to increase theflexibility of the occlusion device 1200 e. For example, the thicknessof the struts 1210 e near or at the central portion 1205 e can be lessthan the thickness of the struts 1210 e near or at the ends of theocclusion device 1200 e.

FIGS. 14A to 14U illustrate alternative central portions 1205 e forimparting sufficient flexibility. For example, as shown in FIGS. 14A and14B, one or more of the struts 1410 at the central portion 1205 e canhave a sinusoidal shape to permit the occlusion device 1200 e to conformto an arcuate portion of the vessel. Each of the struts 1410 can beshaped such that they are nested when the occlusion device 1200 e is inthe constrained configuration. As shown in FIG. 14B, adjacent struts1410 can have varying radii of curvature. For example, the struts 1410can have an increasing radii of curvature around a circumference of thecentral portion 1205 e (compare struts 1410 a, 1410 b, 1410 c shown inFIGS. 14C to 14E).

FIGS. 14F to 14I illustrate a central portion 1205 e with a series ofcutouts (e.g., such as a spiral cut 1470 or a plurality of slots 1460)to allow the occlusion device 1200 e to bend, while still maintainingthe patency of the guidewire lumen. For example, the central portion1205 e can include two arrays of slots 1460 a, 1460 b extendinglongitudinally across the bare metal hub 1205 e′. Each array 1460 a,1460 b can have three slots 1460 (or two, four, five, or more) Each ofthe slots 1416 can extend at least partially around a circumference ofthe bare metal hub 1205 e′. FIGS. 14H and 14I illustrate an alternativeslot configuration 1460. As shown in FIG. 141, adjacent slots 1460 canbe staggered, rather than form separate arrays (as shown in FIG. 14G).

FIGS. 14J and 14K illustrate a central portion 1205 e formed from aseries of interlocking rings 1462. Each of the rings, e.g., 1462 a, hasa number of projections 1472 and indentations 1474 to interface with theadjacent ring 1462 b.

FIGS. 14L and 14M illustrate another occlusion device 1200 e having aspiral-shaped cut 1470 extending around the hub 1205 e′, such that thehub 1205 e′ forms a coil.

FIGS. 14N to 14Q illustrate a central portion 1205 e formed from twointerconnected hook structures 1468 a, 1468 b (see FIG. 14Q) that jointhe first end portion 1202 e′ with the second end portion 1204 e′. Acover portion 1464 can surround the interconnected hook structures 1468a, 1468 b.

FIGS. 14R and 14S illustrate a central portion 1205 e with struts 1480extending from the central hub 1205 e′ that are heat treated to formcoils to provide flexibility to the central portion.

FIGS. 14T and 14U illustrate a central portion 1205 e with struts 1482extending from the central hub 1205 e′. Unlike the strut pattern shownin FIGS. 12A to 13F, the struts 1482 at the central portion 1205 e arepositioned to form cell strutures 1212 e similar to the remainingportions of the lobes 1202 e, 1204 e, as opposed to a star pattern (seeFIG. 12H). There are an increasing number of cells 1212 e from thecentral portion 1205 e toward the ends of the occlusion device 1200 e(e.g., circumferential ring C1 has fewer cells 1212 e thancircumferential ring C2 and circumferential ring C2 has fewer cells 1212e than circumferential ring C1) (see FIG. 14U). This cell patternreduces any kinking at the central portion 1205 e when the occlusiondevice 1200 e is deployed in a curved vessel.

Laser Cut, Football-Shaped Occlusion Device

FIG. 15A illustrates an occlusion device 1500 having a first end portion1502, a second end portion 1504, and a central portion 1505 extendingbetween the first and second end portions 1502, 1504. The occlusiondevice 1500 can have a generally cylindrical central portion 1505 andtapered first and second end portions 1502, 1504, such that a diameterof the central portion 1505 is greater than a diameter of the first andsecond end portions 1502, 1504. The central portion 1505 can extendacross at least about 50% of the length of the occlusion device 1500,such as between about 50% and about 60%. The first end portion 1502 cangenerally refer to the distal end portion of the occlusion device 1500and the second end portion 1504 can generally refer to the proximal endportion of the occlusion device 1500 when the occlusion device isintroduced into the patient.

The occlusion device 1500 can include an expandable frame 1506 and amembrane 1508 carried by the expandable frame 1506. The expandable frame1506 can define a lumen therethrough to facilitate delivery of theocclusion device 1500 over a guide wire. Further, the expandable frame1506 can have a wall thickness of less than or equal to about 0.003inches, such as about 0.002 inches.

The expandable frame 1506 can include a plurality of interconnectedstruts 1510 that can be laser cut from a Nitinol hypotube.Advantageously, the laser cut design can help reduce foreshortening.

As shown in FIG. 15A, the struts 1510 can be at least partially curvedand form a plurality of generally rhombus-shaped open areas 1512.Portions of the expandable frame 1506 on which hydraulic pressure wouldforce the expandable frame 1506 inward can be more porous to inhibitblood-induced occlusion. Further, the struts 1510 at the second endportion 1504 can narrow toward a collar 1516 having a diameter sized fordelivery over a guidewire. The collar 1516 can include an interlockfeature 1518 according to any of the interlock assemblies describedherein.

The expandable frame 1506 can be at least partially covered by a thinmembrane 1508 (e.g., between about 10 microns and about 30 micronsthick). The membrane 1508 should be sufficiently thick to facilitateocclusion, while still minimizing the profile of the occlusion device1500.

The membrane 1508 can be applied to the expandable frame 1506 in amanner that encapsulates at least some of the struts 1510, such that themembrane 1508 is present along both an interior surface and an exteriorsurface of the expandable frame 1506. Possible methods of applying themembrane 1508 are described in further detail below.

As shown in FIG. 15A, the membrane 1508 can cover at least one end ofthe expandable frame 1506 and extend across at least a partial length ofthe expandable frame 1506. In some embodiments, the membrane 1508 atleast coats a portion of the occlusion device 1500 that is concave tothe direction of the blood flow, which can be more occlusive and resistmore migration than occlusion devices that only coat a surface convex tothe direction of the blood flow. For example, the membrane 1508 cancover the first end portion 1502 and extend across at least a portion ofthe central portion 1505, or even at least a majority of the centralportion 1505. For example, the membrane 1508 can extend across at leastabout 50% and/or less than or equal to about 75% of the expandable frame1506, such as between about 60% and about 70%. Although not shown, insome examples, the membrane 1508 can cover both the first and second endportions 1502, 1504 of the expandable frame 1506 and extend along atleast a portion of the central portion 1505.

The membrane 1508 can be positioned on portions of the expandable frame1506 which incline radially outwardly in an upstream direction on whichhydraulic pressure will force the expandable frame 1506 outward. In someembodiments, portions of the expandable frame 1506 that incline radiallyoutward in an upstream direction where the hydraulic pressure wouldforce the expandable frame 1506 inward are not coated.

After the occlusion device 1500 has been deployed, the occlusion device1500 can resist migration (e.g., migrate less than about 5.0 mm from thedeployed position, preferably less than about 4.0 mm, or less than about2.0 mm) under pressures of at least about 100 mmHg and/or less than orequal to about 200 mmHg, for example, between about 150 mmHg and about200 mmHg, such as about 180 mmHg, as determined by the MigrationProtocol described below.

When the occlusion device 1500 is deployed in the vessel, the occlusiondevice 1500 can occlude at least about 80% of blood flow within 30seconds, at least about 90% of blood flow within about 3 minutes, and/orat least about 100% of blood flow within about 5 minutes, withoutreliance on biological processes. In some implementations, the occlusiondevice 1500 can include complete occlusion within about two minutes orwithin about one minute. Using the Occlusion Protocol described below,the occlusion device 1500 can limit the flow rate through a vessel to200 cc/min at 20 mmHg, such as to between about 50 cc/min and about 100cc/min, preferably less than about 50 cc/min at 20 mmHg. Further, theocclusion device 1500 can limit the flow rate through a vessel to 400cc/min at 60 mmHg, such as to between about 100 cc/min and about 150cc/min at 60 mmHg, preferably less than about 125 cc/min at 60 mmHg. Theocclusion device 1500 can limit the flow rate through a vessel to about600 cc/min at about 100 mmHg, such as to between about 175 cc/min andabout 225 cc/min, preferably less than about 200 cc/min at about 100mmHg.

Additionally, a single occlusion device 1500 can be used to treat a widerange of vessels. For example, the occlusion device 1500 can have anexpansion range of at least about 2.0 mm and/or less than or equal toabout 10.0 mm, such as at least about 3.0 mm, at least about 4.0 mm, orat least about 5.0 mm. For instance, a single occlusion device 1500 cantreat vessels having a diameter between about 2.5 mm and about 8.0 mm.Using a single occlusion device 1500 to treat a wide range of vesselscan be desirable to reduce the total stock of occlusion devices thatmust be kept on hand, and the ability to occlude large vessels with asingle occlusion device 1500 can reduce costs.

Further, the single occlusion device 1500 having an expansion range ofat least about 2.0 mm and can have less than 20 percent elongation whenmoving from the unexpanded configuration to the expanded configuration,preferably less than about 15 percent. Minimizing elongation can helpensure accurate positioning of the occlusion device 1500.

The expansion ratio of the occlusion device 1500 can be between about5:1 to about 10:1, such as at least about 5:1, at least about 6:1, atleast about 7:1, at least about 8:1, or at least about 9:1. In someimplementations, the expansion ratio can be at least about 10:1. Inother words, a diameter of the occlusion device 1500 in theunconstrained expanded configuration can be between about five times andabout ten times greater than the diameter of the occlusion device 1500in the unexpanded configuration, such as at least about five times, atleast about six times, at least about seven times, at least about eighttimes, or at least about nine times. In some implementations, thediameter of the expanded configuration can be at least about ten timesgreater than the diameter of the unexpanded configuration. The expansionratio of the occlusion device 1500 is sufficiently large that theocclusion device 1500 is capable of compressing to a minimum sizesuitable for delivery through a catheter having a diameter of less thanabout 5 F, thereby minimizing trauma to the vessel during delivery.Further, the expansion ratio of the occlusion device 1500 issufficiently large that a single, expanded occlusion device is capableof preventing substantially all fluid from flowing past the occlusiondevice in the target vessel.

In the unconstrained expanded state, the occlusion device 1500 can havea diameter that is between about 30% and about 50% larger than thevessel diameter. For vessels sized between about 2.0 mm and about 8.5 mmin diameter, the diameter of the expanded occlusion device 1500 can beat least about 2.6 mm and/or less than or equal to about 12.75 mm,preferably at least about 8.0 mm.

Laser Cut, Tulip-Shaped Occlusion Device

FIG. 16 illustrates an occlusion device 1600 having a substantiallycylindrical body 1605. The cylindrical body 1605 can have an open firstend 1602 and a second end 1604 formed by struts 1610 extending toward acollar 1616, such that the occlusion device 1600 forms a closed end ortulip shape. The first end 1602 can generally refer to the distal end ofthe occlusion device 1600 and the second end 1604 can generally refer tothe proximal end of the occlusion device 1600 when the occlusion deviceis introduced into the patient.

The occlusion device 1600 can include an expandable frame 1606 and amembrane (not shown) carried by the expandable frame 1606. Theexpandable frame 1606 can define a lumen therethrough to facilitatedelivery of the occlusion device 1600 over a guide wire. Further, theexpandable frame 1606 can have a wall thickness of less than or equal toabout 0.003 inches. As mentioned above, the struts 1610 can narrowtoward a collar 1616 having a diameter sized for delivery over aguidewire. The collar 1616 can include an interlock feature 1618according to any of the interlock assemblies described herein.

The expandable frame 1606 can include a plurality of interconnectedstruts 1610 that can be laser cut from a Nitinol hypotube. As shown inFIG. 16, the struts 1610 can be at least partially curved and form aplurality of generally rhombus-shaped open areas 1612. Advantageously,the laser cut design can help reduce foreshortening.

The expandable frame 1606 can be at least partially covered by a thinmembrane 1608 (e.g., between about 10 microns and about 30 micronsthick). The membrane 1608 should be sufficiently thick to facilitateocclusion, while still minimizing the profile of the occlusion device1600. The membrane 1608 can be applied to the expandable frame 1606 in amanner that encapsulates at least some of the struts 1610, such that themembrane 1608 is present along both an interior surface and an exteriorsurface of the expandable frame 1606. Possible methods of applying themembrane 1608 are described in further detail below.

The membrane 1608 can be positioned on portions of the expandable frame1606 on which hydraulic pressure will force the expandable frame 1606outward. In some embodiments, portions of the expandable frame 1606where the hydraulic pressure would force the expandable frame 1606inward are not coated.

Laser Cut, Umbrella-Shaped Occlusion Device

FIG. 17 illustrates an occlusion device 1700 having a wedge-shaped firstend portion 1702, a second end portion 1704, and a central portion 1705therebetween. The first end portion 1702 can have a generally increasingdiameter from the central portion 1705 to the end of the occlusiondevice 1700. The angle of the first end portion 1702 can be optimized totranslate axial force directed at a surface of the first end portion1702 into radial outward force to resist migration. Unlike the first endportion 1702, at least a portion of the second end portion 1704 can besubstantially cylindrical (e.g., having a substantially uniformdiameter).

The first end portion 1702 can generally refer to the distal end portionof the occlusion device 1700 and the second end portion 1704 cangenerally refer to the proximal end portion of the occlusion device 1700when the occlusion device 1700 is introduced into the patient. In thisconfiguration, the second end portion 1704 provides a concave surface tothe direction of the blood flow.

The occlusion device 1700 can include an expandable frame 1706 and amembrane 1708 carried by the expandable frame 1706. The expandable frame1706 can define a lumen therethrough to facilitate delivery of theocclusion device 1700 over a guide wire. Further, the expandable frame1706 can have a wall thickness of less than or equal to about 0.003inches.

The expandable frame 1706 can include a plurality of interconnectedstruts 1710 that can be laser cut from a Nitinol hypotube. As shown inFIG. 17, the struts 1710 can be at least partially curved and form aplurality of generally rhombus-shaped open areas 1712. Advantageously,the laser cut design can help reduce foreshortening.

Additionally, the expandable frame 1706 can be at least partiallycovered by a thin membrane 1708 (e.g., between about 10 microns andabout 30 microns thick). The membrane 1708 should be sufficiently thickto facilitate occlusion, while still minimizing the profile of theocclusion device 1700. The membrane 1708 can be applied to theexpandable frame 1706 in a manner that encapsulates at least some of thestruts 1710, such that the membrane 1708 is present along both aninterior surface and an exterior surface of the expandable frame 1706.Possible methods of applying the membrane 1708 are described in furtherdetail below.

As shown in FIG. 17, the membrane 1708 can cover at least one end of theexpandable frame 1706 and extend across at least a partial length of theexpandable frame 1706. In some embodiments, the membrane 1708 coats atleast a portion of the occlusion device 1700 that is concave to thedirection of the blood flow, which can be more occlusive and resist moremigration than occlusion devices that only coat a surface convex to thedirection of the blood flow. For example, the membrane 1708 can coverthe second end portion 1704 and the first end portion 1702 can be a bareframe. When the bare first end portion 1702 is deployed before thecovered second end portion 1704, the bare first end portion 1702 can atleast partially anchor the occlusion device 1700 in the vessel beforedeploying the covered second end portion 1704, which facilitates preciseplacement of the occlusion device 1700.

The membrane 1708 can be positioned on portions of the expandable frame1706 on which hydraulic pressure will force the expandable frame 1706outward. In some embodiments, portions of the expandable frame 1706where the hydraulic pressure would force the expandable frame 1706inward are not coated.

After the occlusion device 1700 has been deployed, the occlusion device1700 can resist migration (e.g., migrate less than about 5.0 mm from thedeployed position, preferably less than about 4.0 mm, or less than about2.0 mm) under pressures of at least about 100 mmHg and/or less than orequal to about 300 mmHg, for example, between about 100 mmHg and about300 mmHg, such as about 250 mmHg, as determined by Migration Protocoldescribed below.

When the occlusion device 1700 is deployed in the vessel, the occlusiondevice 1700 can occlude at least about 80% of blood flow within 30seconds, at least about 90% of blood flow within about 3 minutes, and/orat least about 100% of blood flow within about 5 minutes, withoutreliance on biological processes. In some implementations, the occlusiondevice 1700 can include complete occlusion within about two minutes orwithin about one minute. Using the Occlusion Protocol described below,the occlusion device 1700 can limit the flow rate through a vessel to200 cc/min at 20 mmHg, such as to between about 100 cc/min and about 150cc/min, preferably less than or equal to about 110 cc/min at 20 mmHg.Further, the occlusion device 1700 can limit the flow rate through avessel to 400 cc/min at 60 mmHg, such as to between about 150 cc/min andabout 200 cc/min at 60 mmHg, preferably less than about 175 cc/min at 60mmHg. The occlusion device 1700 can limit the flow rate through a vesselto about 600 cc/min at about 100 mmHg, such as to between about 175cc/min and about 225 cc/min, preferably less than about 200 cc/min atabout 100 mmHg.

Additionally, a single occlusion device 1700 can be used to treat a widerange of vessels. For example, the occlusion device 1700 can have anexpansion range of at least about 2.0 mm and/or less than or equal toabout 10.0 mm, such as at least about 3.0 mm, at least about 4.0 mm, orat least about 5.0 mm. For instance, a single occlusion device 1700 cantreat vessels having a diameter between about 2.5 mm and about 8.0 mm.Using a single occlusion device 1700 to treat a wide range of vesselscan be desirable to reduce the total stock of occlusion devices thatmust be kept on hand, and the ability to occlude large vessels with asingle occlusion device 1700 can reduce costs.

Further, the single occlusion device 1700 having an expansion range ofat least about 2.0 mm and can have less than 20 percent elongation whenmoving from the unexpanded configuration to the expanded configuration,preferably less than about 15 percent. Minimizing elongation can helpensure accurate positioning of the occlusion device 1700.

The expansion ratio of the occlusion device 1700 can be between about5:1 to about 10:1, such as at least about 5:1, at least about 6:1, atleast about 7:1, at least about 8:1, or at least about 9:1. In someimplementations, the expansion ratio can be at least about 10:1. Inother words, a diameter of the occlusion device 1700 in the expandedconfiguration can be between about five times and about ten timesgreater than the diameter of the occlusion device 1700 in the unexpandedconfiguration, such as at least about five times, at least about sixtimes, at least about seven times, at least about eight times, or atleast about nine times. In some implementations, the diameter of theexpanded configuration can be at least about ten times greater than thediameter of the unexpanded configuration. The expansion ratio of theocclusion device 1700 is sufficiently large that the occlusion device1700 is capable of compressing to a minimum size suitable for deliverythrough a catheter having a diameter of less than about 5 F, therebyminimizing trauma to the vessel during delivery. Further, the expansionratio of the occlusion device 1700 is sufficiently large that a single,expanded occlusion device is capable of preventing substantially allfluid from flowing past the occlusion device in the target vessel.

In the expanded state, the occlusion device 1700 can have a diameterthat is between about 30% and about 50% larger than the vessel diameter.For vessels sized between about 2.0 mm and about 8.5 mm in diameter, thediameter of the expanded occlusion device 1700 can be at least about 2.6mm and/or less than or equal to about 12.75 mm, preferably at leastabout 8.0 mm.

Radiopacity

It can be clinically desirable for any of the occlusion devicesmentioned above to include one or more radiopaque markers. For example,the occlusion device can include one or more tubular markers positionedalong a length of the expandable frame. The marker can have an outerdiameter that is less than or equal to a diameter of the tube from whicha laser cut expandable frame is formed. Use of the tubular marker can beespecially advantageous for occlusion devices having a collar. Thetubular marker 15141514 can be slid from a distal end of the occlusiondevice 1500 towards the collar 1516 on the second end portion 1504 orcentral portion 1505 of the occlusion device (see FIG. 15A). Since anouter diameter of the collar 1516 is larger than an inner diameter ofthe tubular marker 1514, the collar 1516 prevents the tubular marker1514 from moving proximally. Further, the expanded central portion 1505of the occlusion device prevents the band 1514 from moving distally. Insome embodiments, the occlusion device can include a ringlet (not shown)for receiving the tubular marker 1514. Optionally, the marker 1514 canbe held in place using an adhesive and/or a rivet.

As another example, as shown in FIG. 12A, a tubular marker 1214 a can bepositioned around a central portion 1205 a, such that the expanded firstand second end portions 1202 a, 1204 a prevent migration of the tubularmarker 1214 a.

In either example, the shape of the expandable frame fully constrainsthe tubular marker without crimping the marker to the frame, whichreduces stress applied to the underlying frame. Further, since thediameter of the tubular markers is no greater than the outer diameter ofthe occlusion device, the tubular markers do not increase the deliveryprofile of the occlusion device. In certain aspects, a coating can beapplied over the tubular markers.

In some embodiments, at least one radiopaque marker (e.g., two, three,or four) can be positioned (e.g., crimped, press-fit) on at least oneend of the expandable frame. For example, one radiopaque marker 1214′can be positioned at the second end portion 1204′ of the occlusiondevice 1200 a′ (see FIG. 12B), and another radiopaque marker can bepositioned at the second end portion of the occlusion device (notshown). Positioning these markers on the ends of an occlusion devicehaving expanding ends (e.g., occlusion device 1200 a-1) facilitatesvisualization of the occlusion device moving between the compressed andexpanded configurations. FIGS. 2Q and 2R illustrate another occlusiondevice O having markers 242′ that are press-fit onto strut endings ofthe occlusion device O. The markers 242′ can include an aperture 246′and a neck portion 244′ (e.g., a lollipop shape) to facilitate certainretraction capabilities, as described above.

In some embodiments, a radiopaque wire can be wrapped around one or morestruts to form a large marker coil 1514′ (see FIG. 15B). For example,individual struts at the end of an occlusion device 1500′ can be joinedby the marker coil 1514′. Since it can be difficult to insert struts atan end portion of the occlusion device into a tubular marker band, useof the marker coil 1514′ can be especially useful with occlusion deviceshaving narrowed ends (e.g., occlusion device 1500′). The marker coil1514′ can form a substantial marker and secure the struts or strands ata first end portion 1502′. Further, use of the radiopaque wire permitsstorage of a reduced number of spools of wire rather than a large numberof discrete bands. In certain aspects, additional adhesive or heatshrink tubing can be applied to the marker coil to add integrity.

In some embodiments, a fine radiopaque powder can be added to themembrane material to make the entire coating visible. Integrating theradiopaque marker into the coating eliminates the manufacturing step ofhaving to secure a marker to the occlusion device. Alternatively, thefine radiopaque powder can be painted onto the occlusion device or theocclusion device can be dipped into the radiopaque powder.

Methods of Coating the Expandable Frame

In any of the occlusion devices described above, a membrane can bedeposited at least substantially uniformly using an electrospinningprocess. Further, using an electrospinning process, the porosity can becontrolled of the membrane can be controlled to achieve differentproperties. For example, the membrane can be formed having sufficienttensile strength to resist yielding, stretching, or breaking under atleast normal blood pressures, preferably at least about 140 mmHg or 160mmHg. Further, the fibers forming the membrane can have across-sectional diameter between about 5 microns and about 25 microns,such that the membrane can be elongated at least about two to five timesgreater with 25%-75% less force than that of the native material havingthe same thickness. An average pore size can be less than or equal toabout 100 microns or less than or equal to about 50 microns.Additionally, the coated occlusion device can weigh less than or equalto about 1 gram, preferably less than or equal to about 0.6 grams.

In general, the expandable frame can be coated by applying a dissolvedpolymer onto the expandable frame to encapsulate at least some of thestruts or strands. The membrane material can be heated to form a viscousliquid solution that is placed in a syringe. The membrane material canbe advanced by a piston or plunger through a nozzle having one or moreoutlets, where the material flows out onto a rotating mandrel as finefibers. The fine fibers can form a fibrous mat or covering ofbiocompatible covering material on the rotating mandrel. As the membranematerial cools, the fibers solidify, and adjacent, contacting fibers aresintered to one another. Controlling the number of layers of fiber thatare applied to the rotating mandrel provides control over the porosityof membrane.

FIG. 18 is a flow chart illustrating one method 1800 of coating anexpandable frame that can be applied to any of the occlusion devicesdescribed above. The method can include providing a mandrel in the shapeof the expandable frame (block 1802). Optionally, portions of themandrel can be masked to outline the form of an inner coating.Thereafter, an inner coating can be applied to the mandrel using anelectrospinning process (block 1804). When the inner coating iscomplete, the expandable frame can be positioned over the inner coating,such that the expandable frame is in intimate contact with the innercoating (block 1806). If portions of the expandable frame are intendedto remain uncovered, those uncovered portions can be masked beforeapplication of the outer coating (blocks 1808 and 1810). For example,the expandable frame can be masked by loading uncovered portions of theexpandable frame into a tube. The outer coating can adhere to the innercoating to from a single coating that encapsulates at least some ofstruts or strand portions.

Depending on the membrane material, application of the inner coating tothe membrane may be unnecessary. For example, if the membrane includesKynar, a single outer coating can be applied to the expandable framewithout the use of a mandrel. The single outer coating can flow aroundthe struts or strands to encapsulate and adhere to the struts orstrands. Application of the outer coating alone can also be useful forocclusion device designs that may be difficult to position on a mandrel.

The suitability of the membrane can be determined using a number offactors. For example, when visually inspecting the membrane, themembrane should not include any cuts, tears, or large gaps. Further, forat least a Kynar membrane, the membrane should be white or opaque, whichsuggests that the membrane has a porosity and that the membrane issufficiently flexible. As another example, the coated occlusion deviceshould allow less than or equal to about 200 cc/min at 20 mmHg, such asto between about 50 cc/min and about 150 cc/min, preferably less thanabout 130 cc/min, less than about 100 cc/min at 20 mmHg or less thanabout 65 cc/min at 20 mmHg within about five minutes. Further, theocclusion device 1200 a can limit the flow rate through a vessel to nomore than about 400 cc/min at 60 mmHg or no more than about 330 cc/minat 60 mmHg, such as to between about 150 cc/min and about 250 cc/min,preferably less than or equal to about 175 cc/min at 60 mmHg withinabout five minutes. The occlusion device 1200 a can limit the flow ratethrough a vessel to about no more than 600 cc/min at about 100 mmHg or430 cc/min at 100 mmHg, such as to between about 200 mmHg and about 250mmHg, preferably less than about 225 cc/min at about 100 mmHg withinabout five minutes, according to the Occlusion Protocol described below.Additionally, the force to load the coated occlusion device should beless than or equal to about 0.5 lbs.

In some embodiments, the mandrel can have a thin, elongated section thatextends through the center of the occlusion device. When the membrane1208 a is formed, the coating can be applied to the elongated section toproduce a thin extended tubular section of coating 1250 a through whichthe guide wire (e.g., a 0.018″ guidewire) can be introduced (see FIG.12F or 13A). Further, depending on the membrane material, the elongatedinner mandrel can help eliminate irregular buildup of coating on themandrel. The elongated mandrel can also aids in reducing stray chargesfrom carrying the coating away from the mandrel.

Method of Delivering an Occlusion Device

In any of the embodiments disclosed herein configured for over the wiredelivery, a small (e.g., approximately 0.020″) aperture will remain inthe membrane following removal of the guide wire. Occlusion will beprimarily mechanical due to the membrane, but a small blood flow throughthe guidewire aperture will gradually stop via natural biologicalmechanisms. It may be desirable to achieve rapid, essentially completelymechanical occlusion, which can be done by mechanically patching theaperture. This can be accomplished in any of a variety of ways, byplacing an occluder across the aperture. The occluder may take the formof a flap of material attached to the membrane of frame or a plug thatis forced by blood flow into or across the opening following retractionof the guidewire.

The occlusion devices described herein can be advanced to the targetvessel using any of the delivery systems described herein. In use, theaccess to the vasculature can be provided using conventional techniquesthrough an incision on a peripheral artery, such as right femoralartery, left femoral artery, right radial artery, left radial artery,right brachial artery, left brachial artery, right axillary artery, leftaxillary artery, right subclavian artery, or left subclavian artery. Anincision can also be made on right carotid artery or left carotid arteryin emergencies.

The guide wire 128 (e.g., 0.018″ guidewire or smaller) can be deliveredto the target vessel. Thereafter, the delivery system 100, 200 can bedelivered over the guide wire 128 to the target vessel with sufficienttrackability as defined herein. The outer catheter 110, 210 (e.g., 5 For smaller) and the inner catheter 120, 220 can be delivered togetherwith the occlusion device pre-loaded into the delivery system 100, 200.Alternatively, the outer catheter 110, 210 can be delivered first,followed by the inner catheter 120, 220 carrying the occlusion device.Once the delivery system 100, 200 has been delivered to the targetvessel, the inner catheter 120, 220 can move axially until the occlusiondevice extends from the distal end 114, 224 of the outer catheter110,220, as shown in FIG. 3A. In some embodiments, the outer catheter110, 210 can include features shown in FIG. 1B-1 or 2N to deliverycontrast dye and monitor performance of the occlusion device. In someinstances, after the performance assessment, it may be necessary toresheath and reposition the occlusion device to position the occlusiondevice accurately.

The occlusion device can be released from the delivery system 100, 200using any of the techniques described above or any other conventionaltechnique (see e.g., FIGS. 2A to 2K and related discussion).Alternatively, as shown in FIGS. 3D-3F, the support tube 134 can moveaxially to push the occlusion device off the inner catheter 120.Alternatively, the delivery system 100 may utilize any of the interlockassemblies 150, 170, or 180 described herein.

As described above, in some embodiments, the occlusion device caninclude one opened end and one closed end (e.g., covered, structurallyclosed, or otherwise blocked). In some instances, the closed end can bedownstream from the opened end. Preferably, the closed end would be onthe upstream end of the device. This would have the tendency to minimize“wind-socking” of the device due to blood flow forces and would permitthe open downstream end to act as an anchor. Blood pressure on theoccluded upstream end would have the effect of foreshortening the deviceframe, which would secondarily cause an expansion of the distal endaccentuating the anchoring force of the device. This effect isparticularly evident in a braided frame in which the downstream end isopen.

In other embodiments, the occlusion device can include an hourglassdesign (see, e.g., FIG. 12A or 13A). As described above, it can bepreferable to deploy a bare, distal portion prior to deploying acovered, proximal portion. The bare end portion can at least partiallyanchor the occlusion device in the vessel before deploying the coveredsecond end portion, which facilitates precise placement of the occlusiondevice. Further, when the covered end portion is upstream (i.e.,proximal) from the bare end portion, the increase in arterial pressureat the proximal end increases the radially outward forces that can helpthe occlusion device resist migration.

In some instances, as shown in FIG. 2S, the delivery system can includea test balloon 132. Prior to deploying the occlusion device O, the testballoon 132 can be inflated through inflation lumen 134 to occlude thevessel temporarily. After the occlusion device O is delivered, the testballoon 132 can be deflated, and the delivery system can be withdrawn.

In certain variants, the occlusion device can be reinforced using otherreinforcing devices or techniques. For example, one or more coils can bedeployed within the expandable structure. As another example, theexpandable structure can be reinforced with an occlusion balloon. In yetanother example, the method can include ligation to close off the targetvessel.

In Vitro Test Protocols

The performance characteristics of the present disclosure are verifiedusing a series of in vitro test protocols, including: (1) Delivery,Deployment, and Retraction Test Protocol; (2) Acute Migration TestProtocol; (3) Occlusion Effectiveness Test Protocol; and (4) Contrastinjection Test Protocol.

Trackability Test & Delivery Deployment, and Retraction Test

The Delivery, Deployment, and Retraction Test Protocol (“TrackabilityProtocol”) may be used to measure a series of delivery systemperformance characteristics for any of the delivery systems describedherein, including: luer compatibility, pressure integrity, guidewirecompatibility, introducer sheath compatibility, trackability, workinglength, deployment force, embolic re-sheathing, post-deploymentretraction, delivery accuracy, and post-procedure integrity.“Trackability” refers to the relative ability to navigate anendovascular device or delivery system through a tortuous vascularenvironment. As described herein, the Trackability Protocol provides aconsistent, repeatable, in vitro environment in which to evaluate thisdevice characteristic, in addition to the other performance andcompatibility characteristics noted above.

The Trackability Protocol is performed using a Trackability Protocolfixture (see FIG. 19A) comprising a water reservoir 1902, a water heater1904 (e.g., PolyScience Heater model 7306AC1B or equivalent), aperistaltic pump 1906 (e.g., 913 MityFlex Peristaltic Pump S/N P321 orequivalent), anatomical model (“model”) 1908 (e.g., using Modified PAVM1010 with uterine vessel from DialAct Corp. (Asset #4008)), a backpressure column 1910, and the corresponding tubes and connectors. TheTrackability Protocol fixture of FIG. 19 is constructed using thefollowing steps. First, the water reservoir 1902 is filled with water.Second, the water is heated to approximately 97° F. (37° C.), therebysimulating internal human body temperature. Third, the reservoir 1902 isconnected to the peristaltic pump 1906. Fourth, the pump 1906 isconnected in series to the model 1908 using the requisite tubes andconnectors. The model 1908 can include a sheath introducer valve 1916through which the delivery system may be inserted. Fifth, the backpressure column 1910 is connected between an outlet of the model 1912and an inlet of the water reservoir 1914, thereby regulating the fluidpressure within the model. Once the tubes and connectors are secure, thepump 1906 is initiated and water begins to flow through the model 1908to simulate the physiological blood flow rate of the human body.

FIG. 19B illustrates an enlarged view of the Trackability Protocolfixture model 1908 drawn to scale, and FIGS. 19C to 19D illustrateenlarged views of different portions of the model 1908. The model 1908generally consists of a series of vessels to simulate vascular pathways.Dimensions for the model 1908 are provided on the figures. FIG. 19Fillustrates a model 1908′ that includes additional vessels that can beused as the target vessel. Numerals used to identify vessels in model1908 include an apostrophe (′) to identify like vessels in model 1908′.

The Trackability Protocol may be initiated as soon as fluid begins toflow through the model 1908. The Trackability Protocol consists of thefollowing steps. First, the embolic device is loaded into the deliverysystem. At this time, the characteristics of delivery system luercompatibility and delivery system pressure integrity may be evaluated.Luer compatibility may be evaluated by filling a standard 5 cc or 10 ccsyringe with water and connecting the syringe to the proximal luer ofthe delivery system. The syringe may then be evacuated, which flusheswater through the delivery system. If the syringe is capable of beingconnected and disconnected to the delivery system luer, and the deliverysystem is capable of being flushed without bursting or leaking, then thedelivery system may receive a passing grade.

Second, the delivery system is advanced over a 0.018″ guidewire. At thistime, guidewire compatibility may be evaluated. This may be accomplishedby tracking the guidewire through the delivery system until the proximalend of the guidewire extends beyond the proximal end of the deliverysystem. If the guidewire does not buckle or bind during tracking, thenthe delivery system may receive a passing grade.

Third, the delivery system assembly, which now includes the 0.018″guidewire and the embolic device, is inserted into the test fixturethrough a 5 F sheath introducer. At this time, delivery systemcompatibility with the sheath introducer may be evaluated. This may beaccomplished by determining whether the delivery system is capable ofbeing inserted into and through the 5 F sheath introducer.

Fourth, delivery system trackability is assessed. This may beaccomplished by pushing, or “tracking,” the delivery system through themodel 1908. The delivery system is delivered through a sheath introducervalve 1916 and into a model femoral 1932, a model abdominal aorta 1933,a deployment target vessel 1936 (shown as the common hepatic or celiacin model 1908 but can be any other vessel shown in the model for othertrackability tests) and toward a target vessel location 1934 (shown asthe right hepatic but can be any other vessel shown in the model forother trackability tests). An enlarged view of the target vessellocation 1934 is shown in FIG. 19D.

The delivery system is tracked through the model 1908 and toward thetarget vessel 1934 until the delivery system cannot be advanced furtherinto the model 1908. Trackability may then be quantified by measuringthe linear distance between the distal tip of the delivery system to apredefined location in the model. By way of example, FIG. 19G is a photoof a portion of the test fixture 1908. As shown in FIG. 19G, themeasurement is taken from the distal tip of the delivery system 1922 tothe vessel bifurcation point 1944. To achieve a passing grade in themodel embodied in FIG. 19G, the delivery system must be capable oftracking to a linear distance at least 4 cm from (i.e., beyond) thebifurcation 1944.

Fifth, referring back to FIG. 19B, the delivery system is pulledproximal to the target vessel 1934 and into a predefined deploymentvessel 1936. Reference line 1938 represents the target location of theproximal end of the occlusion device.

For detachable and standard pushable devices, deployment force may beevaluated at this time. For detachable devices only, re-sheathingperformance may be evaluated at this time.

Sixth, the occlusion device is fully deployed at the deployment location1938 (or, if possible, tested for partial deployment and retraction asdescribed below). At this time, post-deployment delivery systemretraction may be assessed. This may be accomplished by repositioningthe occlusion device while it is still attached to the delivery system.The maximum acceptable retraction force is 4.5N.

Seventh, the delivery system is detached from the occlusion device andthe delivery system is removed from the model. At this time, occlusiondevice delivery accuracy and post-procedure delivery system integritymay be assessed. Delivery accuracy may be quantified by measuring thedistance from the proximal end of the occlusion device to the referenceline 1938 in the deployment vessel 1936. Delivery system integrity maybe assessed by visually observing the physical condition of the deliverysystem after it has been removed from the Trackability Protocol fixturemodel 1908. If the delivery system has not suffered any obvious kinks,severe bends or curls, or physical breaks or separations, then thedelivery system may receive a passing grade.

Following the trackability test, the model 1908 can be replaced withmodel 1950 to test the delivery, deployment, and retraction of theocclusion device in a T-shaped or B-shaped vessel. The model can beconstructed from polycarbonate with the dimensions of the model labeledon the figure. After the delivery system is advanced over the guidewireand into a 5 F sheath introducer, the delivery system is tracked overthe guidewire through the femoral 1932 and into one of the mock T-shaped(3 mm—1952; 8 mm—1954) or B-shaped vessels (3 mm—1956; 8 mm 1958). Oncein position, the occlusion device can be partially deployed. Before fullrelease, the occlusion device can be resheathed by pulling the occlusiondevice back into the delivery system. The delivery system should be ableto resheath the occlusion device with minimal force, as defined above,and without visible damage to the occlusion device or to the deliverysystem. Thereafter, the full occlusion device is deployed. The targetlocation for the proximal end of the occlusion device is the ostium intothe T-shaped or B-shaped vessel. The distance between the proximal endof the occlusion device and the ostium of the T-shaped 1952′, 1954′ orB-shaped vessel 1956′, 1958′ is measured. To pass, the occlusion devicemust be positioned within 5 mm of the target site (i.e., the ostium).

Acute Migration Test

The Acute Migration Test Protocol (“Migration Protocol”) may be used tomeasure the stability of an implanted occlusion device (e.g., any of theocclusion devices described herein). The term “stability” refers to therelative ability of the occlusion device to withstand fluid pressure andthus maintain its position at a target deployment location.

As shown in FIG. 20A, the Migration Protocol is performed using a testfixture 2000 comprising a water reservoir 2002, a water heater 2004(e.g., PolyScience Heater model 7306AC1B or equivalent), a peristalticpump (or equivalent) 2006 (e.g., 913 MityFlex Peristaltic Pump S/N P321or equivalent), a damping reservoir 2008 (e.g., Air/Oil Reservoir,Grainger item 1U550), a pressure gauge 2010 (e.g., Allheart PressureGauge 20-300 mmHg), a simulated vessel fixture 2012, a simulated vessel2050 (e.g., a 3 mm or 8 mm straight, mock vessel using 1014 Silicone ora curved vessel as shown in FIGS. 20B and 20C), and corresponding tubesand connectors. FIG. 20 shows a schematic of the Migration Protocol testfixture.

FIGS. 20B and 20C illustrate the simulated vessel fixtures 2012positioned in an acrylic stand. The mock 8 mm curved vessel 2030 can beconstructed from silicone and have a 8 mm internal diameter (see FIG.20B). The mock curved vessel 2030 can have a length L of about 85 mm anda width W of about 49 mm. The mock curved vessel 2030 can have a 20 mmradius to centerline of vessel. A tapered, male fitting 2036 can bepositioned at a first end 2032 of the mock vessel for connecting to thetest fixture 2000, and a 5/16 inch, 90 degree elbow fitting 2038 can bepositioned at a second end 2034 of the mock vessel 2030 for connectingto the text fixture 2000.

The mock 3 mm curved vessel 2014 can have a 3 mm internal diameter (seeFIG. 20C). The mock 3 mm curved vessel 2014 can have a length L of about62 mm and a width W of about 19 mm with a 7.5 mm radius to centerline ofvessel. A tapered, male fitting 2020 can be positioned at a first end2016 of the mock vessel for connecting to the test fixture 2000, and a ⅛inch, 90 degree elbow fitting 2022 can be positioned at a second end2018 of the mock vessel 2014 for connecting to the text fixture 2000.

The Migration Protocol test fixture of FIG. 20A is constructed accordingto the following steps. First, the water reservoir 2002 is filled withwater. Second, the water is heated to approximately 97° F. (37° C.),thereby simulating internal human body temperature. Third, an outlet ofthe water reservoir 2002 is connected to the peristaltic pump 2006.Fourth, the pump 2006 is connected in series to the damping reservoir2008 using the requisite tubes and connectors. Fifth, the pressure gauge2010 is connected in distal to the damping reservoir 2008. Finally, thevessel fixture 2012 is connected in series with an inlet of the waterreservoir 2002.

FIG. 20D illustrates an enlarged view of the straight vessel fixture2012. The vessel fixture 2012 generally consists of a tube 2050 definedby a known length and internal diameter. For example, the diameter ofthe tube 2050 used in any given Migration Protocol may vary from 3 mm to10 mm. The migration data recited herein was determined using a tube2050 with a diameter of 3 mm or 8 mm and a length of 15 cm.

The Migration Protocol below is described in connection with the tube2050; however, any one of the vessel fixtures shown in FIGS. 20B and 20Ccan be used. First, an appropriately-sized tube 2050 may be selected.The size of the tube 2050 should correspond to the size of the selectedocclusion device O. Second, the occlusion device O is deployed withinthe tube 2050. Third, the tube 2050 is connected to the vessel fixture2012. Fourth, a reference line R is drawn on the tube 2050 which marksthe proximal end of the occlusion device O inside the tube 2050. Fifth,the pump 2006 is turned on to initiate fluid flow through the MigrationProtocol test fixture 2000 and remove any latent air bubbles. Sixth, avalve 2016 associated with the damping reservoir 2008 is opened to allowapproximately one inch of water to enter the damping reservoir 2008 andthen the valve 2016 is closed. Seventh, the pump speed is slowlyincreased to increase the fluid pressure in the Migration Protocol testfixture 2000. The fluid pressure may be continuously observed using thepressure gauge 2010. The pump speed continues to be increased while themovement of the occlusion device O within the tube 2050 is observed.Finally, at the moment the occlusion device O moves, or “migrates,” morethan 5 mm within the tube 2050, the pressure is recorded. This pressurerepresents the minimum pressure necessary to cause occlusion device Omigration within the tube 2050.

Occlusion Effectiveness Test

The Occlusion Effectiveness Test (“Occlusion Protocol”) may be used tomeasure the efficacy of an implanted occlusion device (e.g., any of theocclusion devices described herein). The term “efficacy” refers to therelative ability of the occlusion device to occlude fluid flow at atarget deployment location.

As shown in FIG. 21, the Occlusion Protocol is performed using a testfixture 2100 comprising a water reservoir 2102, a water heater 2104, aperistaltic pump (or equivalent) 2106 (e.g., PolyScience Heater model7306AC1B or equivalent), a damping reservoir 2108 (e.g., Air/OilReservoir, Grainger item 1U550), a pressure head reservoir 2110, apressure gauge 2112 (e.g., Allheart Pressure Gauge 20-300 mmHg), a lockclip (or valve) 2114, a simulated vessel fixture 2112, a simulatedvessel 2050 (e.g., see FIG. 20D), a volume meter 2120 (e.g., 140 ccsyringe), a two-way stopcock 2122, a timer (or stopwatch) 2124, andcorresponding tubes and connectors. FIG. 21A shows a schematic of theOcclusion Protocol test fixture 2100. The simulated vessel 2150 can beany of the vessels shown in FIGS. 20B to 20C or described in connectionwith test fixture 2000.

The Occlusion Protocol test fixture of FIG. 21 is constructed accordingto the following steps. First, the water reservoir 2102 is filled withwater. Second, the water is heated to approximately 97° F., therebysimulating internal human body temperature. Third, an outlet of thewater reservoir 2102 is connected to the peristaltic pump 2106. Fourth,the pump 2106 is connected in series to the damping reservoir 2108 usingthe requisite tubes and connectors. Fifth, the damping reservoir 2108 isconnected in series to the pressure head 2110, which is connected toboth the water reservoir 2102 and vessel fixture 2112. Sixth, the vesselfixture 2112 is connected to the volume meter 2120, which is controlledwith the stopcock 2122 and drains into the water reservoir 2102.Finally, the pressure gauge 2112 is connected proximal to the vesselfixture 2112 to monitor system pressure.

The vessel fixture 2112 generally consists of a tube 2150 defined by aknown length and internal diameter. For example, the diameter of thetube 2150 used in any given Occlusion Protocol may vary from 3 mm to 10mm. The occlusion data recited herein was determined using a tube 2150with a diameter of 3 mm or 8 mm and a length of 15 cm.

The Occlusion Protocol consists of the following steps. Anappropriately-sized vessel 2150 may be selected. The occlusion device Ois then deployed within the vessel 2150. Although the protocol isdescribed in accordance with the vessel 2150, any of the vessels shownin FIG. 21B or 21C can also be used.

Next, the vessel 2150 is connected to the vessel fixture 2112. The pump2106 is then turned on to initiate fluid flow through the OcclusionProtocol test fixture 2100 and remove any latent air bubbles. Next, avalve 2126 associated with the damping reservoir 2108 is opened to allowapproximately one inch of water to enter the damping reservoir 2108 andthen the valve 2126 is closed. Referring now to FIG. 22B, the pump 2106continues to run until the pressure head reservoir 2110 is filled to thedrain line D. Next, as shown in FIG. 22B, the height H of the pressurehead 2110 is adjusted until the desired pressure H1, H2, H3 is achieved,as indicated on the pressure gauge 2112. Depending on the specific testbeing performed, the desired pressure may range from 20 mmHg H1 to 100mmHg H3. The pump speed is then adjusted to achieve equilibrium betweenthe system pressure, as shown on the pressure gauge 2112, and the fillvolume of the pressure head reservoir 2110. The flow is then stopped byclosing the lock clip 2114 distal to the pressure gauge 2112 andallowing the water to drain from the volume meter 2120. Next, thestopcock 2122 is closed, simultaneously opening the lock clip 2114 andstarting the timer 2124. The timer 2124 should be stopped when thetarget volume in the volume meter 2120 is reached. Finally, the finaltarget volume and time are recorded. Occlusion effectiveness iscalculated by dividing the recorded volume by the recorded time andreporting the outcome as cc/min. For purposes of the Occlusion Protocol,the target volume is arbitrary, however, the target volume must be knownin order to calculate occlusion effectiveness, as described.

Contrast Injection Test

The Contrast Injection Test (“Injection Protocol”) may be used tomeasure the contrast injection performance of a delivery system (e.g.,any of the contrast injection delivery systems described herein).Contrast injection performance quantifies the time required to inject aknown volume of contrast agent through the delivery system. Contrastagent refers to the material, such as Isovue-300 Iopamidol Injection 61%or Optiray-320 Ioversol Injection 68% (or equivalent), that a physicianmay use to visualize the vasculature over the course of an endovascularprocedure. Such visualization is accomplished using standard imagingtechniques.

The Injection Protocol is performed using a test fixture 2300 comprisinga pressure supply 2302 (e.g., a nitrogen tank), a pressure supplyregulator 2304, a cylinder (or piston) 2306 (e.g., a Bimba StainlessSR-0910-D (factor 1.21 to 1)), a contrast reservoir 2308 (e.g., a 25 ccHand Injector), a high pressure three-way stopcock 2310, a volume meter2312 (e.g., a graduated cylinder), a timer (or stopwatch) 2314, contrastsolution 2316, a syringe, a lock clip 2318, and corresponding tubes andconnectors. FIG. 23 shows a schematic of the Injection Protocol testfixture 2300.

The Injection Protocol test fixture of FIG. 23 is constructed accordingto the following steps. The pressure supply 2302 is connected to thepressure regulator 2304, which is then connected to the cylinder 2306.In turn, the cylinder 2306 is connected to the stopcock 2310, which isconnected to the contrast reservoir 2308, which contains contrast agent2316. The stopcock 2310 is also connected to the delivery system 2320.The distal end of the delivery system is placed into the volume meter2312.

The Injection Protocol consists of the following steps. First, 100 mL ofcontrast agent 2316 is prepared by mixing equal parts contrast fluidwith water. Next, the contrast reservoir 2308 is filled with thecontrast agent 2316. The contrast agent 2316 is then transferred to thecylinder 2306 by opening the stopcock 2310 between the cylinder 2306 andcontrast reservoir 2308. Next, the delivery system 2320 is flushed withexcess contrast agent using a standard syringe. Next, the regulator 2304is set to the desired pressure (e.g., 100 psi). The distal tip of thedelivery system 2320 is then sealed using the lock clip 2318 under theassumption that the occlusion device prevents contrast dye from exitingthe distal end of the delivery system. A side port of the deliverysystem 2320 is then connected to the closed end of the three-waystopcock 2310. Next, the stopcock 2310 is turned to connect the deliverysystem 2320 with the cylinder 2306 and pressurize the cylinder 2306. Thepressure regulator 2304 is then adjusted to the desired pressure, basedon the relevant cylinder factor. Of course, the cylinder factor may varydepending on the type of cylinder used. Next, the pressure supplyregulator 2304 is turned and the timer 2314 is simultaneously started.The timer 2314 should be stopped when the target volume in the volumemeter 2312 is reached. Finally, the final target volume and time arerecorded. Injection performance is calculated by dividing the recordedvolume by the recorded time and reporting the outcome in cc/min. Forpurposes of the Injection Protocol, the target volume is arbitrary,however, the target volume must be known in order to calculate contrastinjection rate, as described.

TERMINOLOGY

Conditional language, such as “can,” “could,” “might,” or “may,” unlessspecifically stated otherwise, or otherwise understood within thecontext as used, is generally intended to convey that certainembodiments include, while other embodiments do not include, certainfeatures, elements, and/or steps. Thus, such conditional language is notgenerally intended to imply that features, elements, and/or steps are inany way required for one or more embodiments, whether these features,elements, and/or steps are included or are to be performed in anyparticular embodiment.

The terms “approximately,” “about,” and “substantially” as used hereinrepresent an amount close to the stated amount that still performs adesired function or achieves a desired result. For example, depending onthe context, the terms “approximately”, “about”, and “substantially” mayrefer to an amount that is within less than 10% of, within less than 5%of, within less than 1% of, within less than 0.1% of, and within lessthan 0.01% of the stated amount.

The ranges disclosed herein also encompass any and all overlap,sub-ranges, and combinations thereof. Language such as “up to,” “atleast,” “greater than,” “less than,” “between” and the like includes thenumber recited. Numbers preceded by a term such as “about” or“approximately” include the recited numbers. For example, “about 3 mm”includes “3 mm.”

The ranges provided herein are set forth solely for illustrating typicaldevice dimensions. The actual dimensions of a device constructedaccording to the principles of the present invention may obviously varyoutside of the listed ranges without departing from those basicprinciples. For example, diameter outside of the preferred ranges mayalso be used, provided that the functional consequences of the diameterare acceptable for the intended purpose of the catheter. In particular,the lower limit of the diameter for any portion of catheter body 110 ina given application will be a function of the number of fluid or otherfunctional lumen contained in the catheter, together with the acceptableminimum aspiration flow rate and collapse resistance.

Although certain embodiments and examples have been described herein, itwill be understood by those skilled in the art that many aspects of themethods and devices shown and described in the present disclosure may bedifferently combined and/or modified to form still further embodimentsor acceptable examples. All such modifications and variations areintended to be included herein within the scope of this disclosure. Awide variety of designs and approaches are possible. No feature,structure, or step disclosed herein is essential or indispensable.

Any methods disclosed herein need not be performed in the order recited.The methods disclosed herein include certain actions taken by apractitioner; however, they can also include any third-party instructionof those actions, either expressly or by implication. For example,actions such as “expanding an expandable structure” includes“instructing expansion of an expandable structure.”

Some embodiments have been described in connection with the accompanyingdrawings. However, it should be understood that the figures are notdrawn to scale. Distances, angles, etc. are merely illustrative and donot necessarily bear an exact relationship to actual dimensions andlayout of the devices illustrated. Components can be added, removed,and/or rearranged. Further, the disclosure herein of any particularfeature, aspect, method, property, characteristic, quality, attribute,element, or the like in connection with various embodiments can be usedin all other embodiments set forth herein. Additionally, it will berecognized that any methods described herein may be practiced using anydevice suitable for performing the recited steps.

For purposes of this disclosure, certain aspects, advantages, and novelfeatures are described herein. It is to be understood that notnecessarily all such advantages may be achieved in accordance with anyparticular embodiment. Thus, for example, those skilled in the art willrecognize that the disclosure may be embodied or carried out in a mannerthat achieves one advantage or a group of advantages as taught hereinwithout necessarily achieving other advantages as may be taught orsuggested herein.

Moreover, while illustrative embodiments have been described herein, thescope of any and all embodiments having equivalent elements,modifications, omissions, combinations (e.g., of aspects across variousembodiments), adaptations and/or alterations as would be appreciated bythose in the art based on the present disclosure. The limitations in theclaims are to be interpreted broadly based on the language employed inthe claims and not limited to the examples described in the presentspecification or during the prosecution of the application, whichexamples are to be construed as non-exclusive. Further, the actions ofthe disclosed processes and methods may be modified in any manner,including by reordering actions and/or inserting additional actionsand/or deleting actions. It is intended, therefore, that thespecification and examples be considered as illustrative only, with atrue scope and spirit being indicated by the claims and their full scopeof equivalents.

EXAMPLE EMBODIMENTS

The following example embodiments identify some possible permutations ofcombinations of features disclosed herein, although other permutationsof combinations of features are also possible.

1. A vascular occlusion device, comprising:

-   -   a frame comprising a proximal embolic zone and a distal        anchoring zone separated by a hub;    -   the proximal and distal zones self-expandable from a constrained        diameter to an unconstrained diameter of at least about 500% of        the constrained diameter;    -   a guidewire lumen through the hub, to permit placement over a        guidewire; and    -   a valve in communication with the guidewire lumen.

2. The endovascular occlusion device as in Embodiment 1, having anexpansion ratio of at least about 6:1.

3. The endovascular occlusion device as in Embodiment 1, having anexpansion ratio of at least about 7:1.

4. The endovascular occlusion device as in any one of Embodiments 1 to3, having an unconstrained expanded diameter of at least about 1.5 mmand which can be deployed from a 0.7 mm or smaller inside diameterlumen.

5. The endovascular occlusion device as in any one of Embodiments 1 to3, having an unconstrained expanded diameter of at least about 6.0 mmand which can be deployed from a 0.7 mm or smaller inside diameterlumen.

6. The endovascular occlusion device as in any one of Embodiments 1 to5, wherein the device is configured to occlude at least about 90 percentof flow through a vessel when the expandable tubular frame is in anexpanded configuration.

7. An endovascular occlusion device, comprising an expandable occlusiveelement for expansion within and occlusion of a vessel, the occlusiveelement having an expansion ratio of at least about 5:1.

8. A delivery system for delivering an occlusion device, the deliverysystem comprising:

-   -   an outer catheter;    -   an inner catheter axially movable within the outer catheter, the        inner catheter configured to deliver the occlusion device out of        the outer catheter, wherein the occlusion device comprises:        -   an expandable structure configured to move between an            unexpanded configuration and an expanded configuration, the            expandable structure having a proximal portion, a middle            portion, and a distal portion,        -   wherein the expandable structure has an expansion ratio of            at least about 5:1,        -   and wherein the occlusion device is configured to prevent            substantially all fluid from flowing past the occlusion            device when the occlusion device is in the expanded            configuration in the vessel.

9. The delivery system of Embodiment 8, further comprising a supporttube axially disposed between the outer catheter and the inner catheter.

10. The delivery system of Embodiment 8 or 9, wherein the outer catheterincludes an inner diameter of less than or equal to about 2 mm.

11. The delivery system of any one of Embodiments 8 to 10, wherein theinner catheter is configured to carry the expandable structure on adistal portion of the inner catheter.

12. The delivery system of any one of Embodiments 8 to 11, wherein theinner catheter releasably engages at least one of the proximal end orthe distal end of the expandable structure.

13. A method of occluding a vessel, the method comprising:

-   -   advancing a delivery system over a guidewire in the vessel;    -   deploying a single occlusion device from the delivery system,        the single occlusion device having at least one closed end and        an occlusive membrane extending across at least the closed end,        wherein the single occlusion device has an expansion ratio of at        least about 5:1.

14. The method of Embodiment 13, wherein a diameter of the expandablestructure in the unexpanded configuration is less than or equal to about2 mm.

15. The method of Embodiment 13 or 14, wherein the delivery systemcomprises an outer catheter having an inner diameter of less than orequal to about 2 mm.

16. The method of any one of Embodiments 13 to 15, wherein positioningthe delivery system comprises advancing the delivery system over a guidewire.

17. An endovascular occlusion device for occluding blood flow through avessel, comprising:

-   -   an expandable frame; and    -   a membrane carried by the frame;    -   wherein the frame and the membrane are dimensioned for        deployment from a tube having an inside diameter of no more than        about 2 mm, and are expandable to a diameter of at least about 8        mm following deployment from the tube; and the membrane has a        porosity which achieves a reduction in blood flow of at least        about 80% within 5 minutes of deployment from the tube in a        blood vessel.

18. An endovascular occlusion device as in Embodiment 17, configured toachieve a reduction in blood flow of at least about 80% within 2 minutesof deployment from the tube in a blood vessel.

19. An endovascular occlusion device as in Embodiment 18, configured toachieve a reduction in blood flow of at least about 80% within 1 minuteof deployment from the tube in a blood vessel.

20. An endovascular occlusion device as in any one of Embodiments 17 to19, configured to achieve total occlusion within 5 minutes of deploymentfrom the tube in a blood vessel.

21. An endovascular occlusion device as in Embodiment 20, configured toachieve total occlusion within 1 minute of deployment from the tube in ablood vessel.

22. An endovascular occlusion device as in any one of Embodiments 17 to21, having an expansion ratio of at least about 6:1.

23. An endovascular occlusion device as in any one of Embodiments 17 to21, having an expansion ratio of at least about 7:1.

24. An endovascular occlusion device as in any one of Embodiments 17 to23, deliverable over an 0.018 inch guidewire.

25. An endovascular occlusion device as in any one of Embodiments 17 to24, wherein the device has an average COP across a diameter of 2.5 mm to8.0 mm of between about 30 mmHg and about 140 mmHg.

26. An endovascular occlusion device for achieving mechanical occlusionof blood flow in a vessel, without requiring biological processes toachieve occlusion, comprising:

-   -   an expandable support structure, carrying a porous membrane,        wherein the membrane is configured to obstruct blood flow        through the vessel when the support structure is in an expanded        configuration; the membrane having an average pore size of no        more than about 100 microns.

27. An endovascular occlusion device as in Embodiment 26, wherein themembrane comprises an average pore size of no more than about 50microns.

28. An endovascular occlusion device as in Embodiment 26, or 27 whereinthe membrane comprises an average thickness of no more than about 30microns.

29. An endovascular occlusion device as in any one of Embodiments 26 to28, wherein the occlusion device is deliverable from a lumen having aninside diameter of no more than about 2 mm.

30. An endovascular occlusion device as in Embodiment 29, wherein theocclusion device is deliverable from a lumen having an outside diameterof less than or equal to about 1.67 mm.

31. An endovascular occlusion device as in any one of Embodiments 26 to30, deliverable over an 0.018 inch guidewire.

32. An endovascular occlusion device as in any one of Embodiments 26 to31, wherein the device has an average COP across a diameter of 2.5 mm to8.0 mm of between about 30 mmHg and about 140 mmHg.

33. An endovascular occlusion device for occluding blood flow through avessel, the occlusion device comprising a frame that is expandablethrough a range from a first, compressed diameter to a second, maximumexpanded diameter, wherein the range of expansion is sufficient toocclude blood vessels having inside diameters anywhere within the rangefrom about 2.5 mm to about 8 mm.

34. An endovascular occlusion device as in Embodiment 33, wherein therange of expansion is sufficient to occlude blood vessels having insidediameters anywhere within the range from about 2.5 mm to about 8 mm.

35. An endovascular occlusion device as in Embodiment 33 or 34, whereinthe first, compressed diameter is small enough that the occlusion deviceis deployable from a lumen having an inside diameter of no more thanabout 2 mm.

36. An endovascular occlusion device as in Embodiment 35, wherein thefirst, compressed diameter is small enough that the occlusion device isdeployable from a lumen having an outside diameter of less than or equalto about 1.67 mm.

37. An endovascular occlusion device as in Embodiment 36, having anexpansion ratio of at least about 6:1.

38. An endovascular occlusion device as in Embodiment 37, having anexpansion ratio of at least about 7:1.

39. An endovascular occlusion device as in any one of Embodiments 33 to38, deliverable over an 0.018 inch guidewire.

40. An endovascular occlusion device as in any one of Embodiment 33 to39, wherein the device has an average COP across a diameter of 2.5 mm to8.0 mm of between about 30 mmHg and about 140 mmHg.

41. A low crossing profile, high dynamic range endovascular occlusiondevice having an opening for receiving a guidewire therethrough, theocclusion device expandable from a first diameter for transvascularnavigation within a deployment catheter to a deployment site, to asecond diameter for occluding a vessel following deployment from thecatheter, wherein the catheter has a diameter of no greater than about 5French and the expansion ratio is at least about 6×.

42. A low crossing profile, high dynamic range endovascular occlusiondevice as in Embodiment 41, wherein the expansion ratio is at leastabout 8×.

43. A low crossing profile, high dynamic range endovascular occlusiondevice as in Embodiment 41 or 42, comprising an expandable frame and anocclusion membrane.

44. An endovascular occlusion deployment system for navigating tortuousvasculature to deploy an occlusion device at a target site in a vessel,comprising:

-   -   an elongate, flexible tubular body, having a proximal end, a        distal end, and a diameter of no more than about 5 French; and    -   an occlusion device releasably carried in the distal end of the        tubular body, the occlusion device having an expansion ratio of        at least about 5 to 1;    -   wherein the distal end is advanceable to the trackability target        vessel as determined by the test protocol identified in        Trackability Protocol described herein.

45. A low crossing profile, high dynamic range endovascular occlusiondevice with low elongation, the occlusion device expandable from a firstdiameter for transvascular navigation within a deployment catheter to adeployment site, to a second diameter for occluding a vessel followingdeployment from the catheter, wherein the catheter has a diameter of nogreater than about 5 French, the occlusion device has an expansion ratioof at least about 5×, and the elongation of the device between the firstdiameter and the second diameter is no more than about 20%.

46. A migration resistant endovascular occlusion device for occludingblood flow through a vessel, comprising:

-   -   an expandable frame comprising an upstream lobe and a downstream        lobe separated by a neck portion; and    -   a membrane carried by the frame;    -   wherein the frame and membrane are dimensioned for deployment        from a tube having an inside diameter of no more than about 2        mm, and are expandable to a diameter of at least about 8 mm        following deployment from the tube; and    -   wherein the occlusion device exhibits a migration of less than        about 5 mm in 10 minutes as determined by the test protocol        identified in Migration Protocol described herein.

47. An endovascular occlusion deployment system with contrast injectioncapability, for navigating tortuous vasculature to deploy an occlusiondevice at a target site in a vessel, comprising:

-   -   an elongate, flexible tubular body, having a proximal end, a        distal end, and a diameter of no more than about 5 French; and    -   an occlusion device releasably carried in the distal end of the        tubular body, the occlusion device having an expansion ratio of        at least about 5 to 1; and    -   a contrast injection port on the body, proximal to the occlusion        device;    -   wherein the contrast injection port permits injection of        contrast while the occlusion device is in an expanded        configuration and prior to release of the occlusion device from        the tubular body.

48. An endovascular occlusion device for mechanical occlusion of bloodflow in a vessel, comprising:

-   -   a support structure, expandable from a reduced cross section for        transluminal navigation to an enlarged cross section for        occluding a vessel;    -   an upstream lobe on the support structure, separated from a        downstream lobe by a neck portion;    -   a guidewire lumen extending through the neck portion;    -   the upstream lobe comprising a concave configuration which is        concave in a direction away from the downstream lobe;    -   a valve in the guidewire lumen; and    -   a porous membrane carried by the upstream lobe.

49. An endovascular occlusion device as in Embodiment 48, wherein thedownstream lobe comprises a concave configuration, concave in adirection facing away from the upstream lobe.

50. An endovascular occlusion device as in Embodiment 49, wherein theupstream lobe comprises a plurality of side wall struts.

51. An endovascular occlusion device as in Embodiment 50, wherein theside wall struts carry the membrane.

52. An endovascular occlusion device as in any one of Embodiments 48 to51, wherein the valve comprises a collapsible tube extending from theneck portion into the upstream lobe.

53. An endovascular occlusion device as in any one of Embodiments 48 to52, wherein the downstream lobe comprises a plurality of side wallstruts.

54. An endovascular occlusion device as in any one of Embodiments 48 to53, wherein following deployment in an artery with the upstream lobe inan anatomically proximal orientation, blood pressure on the concave sideof the upstream lobe generates a radially outward force from theupstream lobe against the artery wall.

55. An endovascular occlusion device as in Embodiment 54, wherein bloodpressure on the concave side of the upstream lobe generates an axiallydistal force on the neck portion.

56. The endovascular occlusion device as in any one of Embodiments 48 to55, having an expansion ratio of at least about 6:1.

57. The endovascular occlusion device as in any one of Embodiment 48 to55, having an expansion ratio of at least about 7:1.

58. The endovascular occlusion device as in any one of Embodiment 48 to57, having an unconstrained expanded diameter of at least about 6.0 mmand which can be deployed from a 1 mm or smaller inside diameter lumen.

59. The endovascular occlusion device as in any one of Embodiment 48 to58, wherein the device is configured to occlude at least about 90percent of flow through a vessel when the expandable tubular frame is inan expanded configuration.

60. An endovascular occlusion device as in any one of Embodiment 48 to59, configured to achieve a reduction in blood flow of at least about80% within 2 minutes of deployment from the tube in a blood vessel.

61. An endovascular occlusion device as in any one of Embodiment 48 to60, configured to achieve a reduction in blood flow of at least about80% within 1 minute of deployment from the tube in a blood vessel.

62. An endovascular occlusion device as in any one of Embodiment 48 to61, configured to achieve total occlusion within 5 minutes of deploymentfrom the tube in a blood vessel.

63. An endovascular occlusion device as in Embodiment 62, configured toachieve total occlusion within 1 minute of deployment from the tube in ablood vessel.

64. An endovascular occlusion device deployment system, comprising theendovascular occlusion device of any one of Embodiment 48 to 63,oriented on an elongate, flexible deployment catheter having a proximalend and a distal end such that the upstream lobe faces the proximal endof the catheter.

65. A method of occluding a vessel, comprising the steps of:

-   -   deploying an anchoring lobe of an occlusion device in a vessel,        without occluding blood flow;    -   thereafter deploying an occlusion lobe of the device in the        vessel to occlude blood flow;    -   wherein the anchoring lobe is downstream of the occlusion lobe.

66. A method of occluding a vessel as in Embodiment 65, additionallycomprising evaluating the position of the occlusion device in the vesselprior to the deploying an occlusion lobe step.

67. An endovascular occlusion device for occlusion of blood flow in avessel, comprising:

-   -   a support structure, self-expandable from a reduced cross        section for transluminal navigation to an enlarged cross section        for occluding a vessel;    -   the support structure defining a first axially outwardly facing        concavity when in the enlarged configuration, the concavity        having an upstream opening and a downstream end;    -   a guidewire opening in the downstream end; and    -   a collapsible tube extending from the guidewire opening in an        upstream direction into the concavity.

68. An endovascular occlusion device as in Embodiment 67, furthercomprising a membrane carried by the support structure.

69. An endovascular occlusion device as in Embodiment 68, wherein thesupport structure additionally comprises a downstream lobe.

70. An endovascular occlusion device as in Embodiment 69, wherein thedownstream lobe comprises a plurality of struts spaced apart when in theenlarged configuration, to provide a plurality of openings therethrough.

71. An endovascular occlusion device as in Embodiment 70, wherein thestruts define a second concavity, facing in an opposite direction fromthe first, upstream facing concavity.

72. A vascular occlusion device, comprising:

-   -   a frame comprising a proximal lobe and a distal lobe separated        by a hub;    -   the proximal and distal lobes self-expandable from a constrained        diameter to an unconstrained diameter of at least about 500% of        the constrained diameter;    -   a hinge on the hub, to permit relative lateral deflection of the        proximal and distal lobes to allow the frame to conform to a        curved vessel; and    -   an embolic membrane carried by the proximal lobe.

73. A vascular occlusion device as in Embodiment 72, wherein the hingecomprises at least one slot in a side wall of the hub.

74. A vascular occlusion device as in Embodiment 72, wherein the hingecomprises a spiral slot in a side wall of the hub.

75. A vascular occlusion device as in any one of Embodiments 72 to 74,further comprising a guidewire lumen extending through the hub.

76. A vascular occlusion device as in Embodiment 75, further comprisingan occluder for occluding the guidewire lumen.

77. A vascular occlusion device as in Embodiment 76, wherein theoccluder comprises a membrane configured to occlude the guidewire lumenfollowing removal of a guidewire.

78. A vascular occlusion device as in Embodiment 77, wherein theoccluder comprises a tubular membrane having a central lumen forremovably receiving a guidewire.

79. A vascular occlusion device as in Embodiment 78, wherein the tubularmembrane is connected to the embolic membrane.

80. A vascular occlusion device as in Embodiment 78, wherein the tubularmembrane is integrally formed with the embolic membrane.

81. A vascular occlusion device as in Embodiment 78, wherein the tubularmembrane has a first end which is anchored with respect to the hub, anda free end spaced apart from the anchored end.

82. A vascular occlusion device as in Embodiment 81, wherein the tubularmembrane is invertible, such that the free end can be moved between thedistal lobe and the proximal lobe.

83. A vascular occlusion device as in Embodiment 81, wherein the distallobe has a distal landing zone and a proximal tapered zone which tapersradially inwardly in the proximal direction to permit retraction of thedistal lobe into a tubular sheath.

84. A vascular occlusion device as in any one of Embodiments 72 to 83,wherein the embolic membrane is concave in the proximal direction.

85. A vascular occlusion device as in Embodiment 84, wherein the embolicmembrane extends along an axis between a distal apex and a proximalopening, and the length of the membrane measured along the axis is nomore than about 50% of the length of the device.

86. A vascular occlusion device as in Embodiment 85, wherein the lengthof the membrane measured along the axis is no more than about 40% of thelength of the device.

87. A vascular occlusion device, comprising:

-   -   a frame comprising a proximal embolic zone and a distal        anchoring zone separated by a hub;    -   the proximal and distal zones self-expandable from a constrained        diameter to an unconstrained diameter of at least about 500% of        the constrained diameter;    -   a guidewire lumen through the hub, to permit placement over a        guidewire; and    -   a valve in communication with the guidewire lumen.

What is claimed is:
 1. An endovascular occlusion device for occlusion ofblood flow in a vessel, comprising: a support structure, self-expandablefrom a reduced cross section for transluminal navigation to an enlargedconfiguration for occluding a vessel; the support structure defining afirst axially outwardly facing concavity when in the enlargedconfiguration, the first axially outwardly facing concavity having anupstream opening and a downstream end; a guidewire opening in thedownstream end; and a collapsible tube extending from the guidewireopening in an upstream direction into the first axially outwardly facingconcavity.
 2. An endovascular occlusion device as in claim 1, furthercomprising a membrane carried by the support structure.
 3. Anendovascular occlusion device as in claim 2, wherein the supportstructure comprises an upstream lobe that defines the first axiallyoutwardly facing concavity, and wherein the support structureadditionally comprises a downstream lobe.
 4. An endovascular occlusiondevice as in claim 3, wherein the downstream lobe comprises a pluralityof downstream lobe struts spaced apart when in the enlargedconfiguration, to provide a plurality of openings therethrough.
 5. Anendovascular occlusion device as in claim 4, wherein the downstream lobestruts define a second concavity, facing in an opposite direction fromthe first axially outwardly facing concavity.
 6. An endovascularocclusion device as in claim 4, wherein expansion of the downstream lobepermits flow between the downstream lobe struts.
 7. An endovascularocclusion device as in claim 4, wherein the upstream lobe comprises aplurality of upstream lobe struts.
 8. An endovascular occlusion deviceas in claim 7, wherein the membrane extends between the plurality ofupstream lobe struts to occlude flow between the upstream lobe strutsupon expansion of the upstream lobe.
 9. An endovascular occlusion deviceas in claim 3, wherein the upstream lobe is expandable to include aplurality of upstream lobe struts having a first laterally outwardfacing concave structure, and wherein the downstream lobe is expandableto include a plurality of downstream lobe struts having a secondoutwardly concave structure.
 10. An endovascular occlusion device as inclaim 9, wherein a radius of a first best fit circle conforming to thefirst laterally facing concave structure is less than a radius of asecond best fit circle conforming to the second outwardly concavestructure, the second best fit circle being measured at a samecircumferential position as the first best fit circle.
 11. Anendovascular occlusion device as in claim 3, wherein the upstream lobeand the downstream lobe are separated by a hub.
 12. An endovascularocclusion device as in claim 11, wherein the hub is flexible to allowbending between the upstream and downstream lobes.
 13. An endovascularocclusion device as in claim 11, wherein the hub is partiallyexpandable.
 14. An endovascular occlusion device as in claim 3, whereinthe downstream lobe comprises an open distal end.
 15. An endovascularocclusion device as in claim 3, wherein when in the enlargedconfiguration, the occlusion device has bilateral asymmetry across aplane extending between the upstream lobe and the downstream lobe. 16.An endovascular occlusion device as in claim 1, wherein when in theenlarged configuration, the occlusion device has bilateral asymmetry.17. An endovascular occlusion device as in claim 1, having an expansionratio of at least about 5:1.
 18. An endovascular occlusion device as inclaim 1, having an expansion ratio of at least about 6:1.
 19. Anendovascular occlusion device as in claim 1, having an expansion ratioof at least about 7:1.
 20. An endovascular occlusion device as in claim1, wherein the device is configured to occlude at least about 90 percentof flow through a vessel when the support structure is in an expandedconfiguration.
 21. An endovascular occlusion device as in claim 1,wherein a maximum expanded diameter of the support structure is at theupstream opening.